bluuebunny/crossref_metadata_2025 huggingface dataset:
Alpha‐adrenergic inhibition of rat cerebellar Purkinje cells in vitro: a voltage‐clamp study.
Authors: Crepel F , Debono M , Flores R
Published: December 2015

1. The effects of the alpha 2‐adrenergic agonist clonidine on the membrane properties of Purkinje cells were analysed in sagittal slices of adult rat cerebellum by the use of intracellular recordings performed at a somatic level in the single‐electrode voltage‐clamp mode. 2. In preliminary current‐clamp experiments, clonidine elicited in all cells a hyperpolarization 3‐8 mV in amplitude, accompanied by a 15‐35% increase of the input resistance when it was added to the bath at a concentration of 2‐5 microM. 3. In voltage‐clamped cells at a potential of ‐65 mV. the same concentration of clonidine always induced an outward shift of the holding current (0.2‐0.5 nA in amplitude), thus corresponding to the hyperpolarization seen in current‐clamp experiments, and this effect was accompanied by a clear increase of membrane resistance. Furthermore, clonidine markedly depressed the inward relaxations induced by hyperpolarizing commands of amplitude less than 10‐20 mV whereas those induced by larger steps were much less affected. All these effects of clonidine were reversible when the drug was washed out. 4. When the slices were bathed in a medium containing 10 mM‐Cs and 5 X 10(‐6) M‐tetrodotoxin, the inward relaxations induced by hyperpolarizing steps were abolished. However, a small inward current was still present when the membrane potential was stepped back to ‐65 mV, which was in turn blocked by the Ca‐channel blocker Cd. This inward Ca current was also blocked by 2‐5 microM‐clonidine in the bath. 5. All these effects of clonidine were abolished by the alpha 1‐adrenergic antagonists prazosin and phentolamine at concentrations of 0.5 and 40 microM respectively in the bath. In contrast, they were only weakly antagonized or unaffected by 2 microM of the alpha 2‐adrenergic antagonist yohimbine. 6. On the basis of these results and of a previous work on the ionic basis of the inward rectification of Purkinje cells (Crepel & Penit‐Soria, 1986), it appears that these neurones exhibit a well developed alpha (possibly alpha 1)‐adrenergic inhibition of a low‐threshold Ca conductance and a Ca‐dependent K conductance operating near resting potential.
The response of hair cells in the basal turn of the guinea‐pig cochlea to tones.
Authors: Cody A R , Russell I J
Published: December 2015

1. Intracellular recordings were made from inner and outer hair cells in the basal turn of the guinea‐pig cochlea. The resting membrane potentials of the inner hair cells are more positive than ‐50 mV while those of outer hair cells are usually more negative than ‐70 mV. 2. At low frequencies the receptor potentials of inner hair cells are predominantly depolarizing while those from outer hair cells are hyperpolarizing at low and moderate sound pressure (e.g. less than 90 dB re 2 X 10(‐5) Pa at 600 Hz). The potentials then become predominantly depolarizing at high sound pressure. 3. The asymmetry of the inner and outer hair cell receptor potentials are manifested instantaneously except at high stimulus levels when the depolarizing responses of outer hair cells take several cycles to develop. 4. At the offset of intense tones outer hair cell membrane potentials remain depolarized by 1‐2 mV above their resting value and return to normal over a period depending on the level and duration of the tone. 5. In response to tones above about 2 kHz and at levels below about 90 dB the wave forms of outer hair cell receptor potentials are virtually symmetrical without measurable d.c. components. In response to tones close to their best frequencies (16‐21 kHz), inner hair cells in the basal turn generate large depolarizing (d.c.) receptor potentials while outer hair cells from this region of the cochlea do not generate significant voltage responses. 6. Frequency tuning curves were derived for inner and outer hair cells from the amplitude‐intensity relationships of their d.c. and phasic (a.c.) receptor potentials respectively. When the latter were compensated for the low‐pass characteristics of the recording system and the hair cell time constant, the frequency selectivity of inner and outer hair cells are similar. 7. The response properties of inner and outer hair cells in the basal turn of the guinea‐pig cochlea are discussed in relation to their proposed roles in mechano‐electric transduction.
Evidence for separate mechanisms of induction of biphasic fever inside and outside the blood‐brain barrier in rabbits.
Authors: Morimoto A , Murakami N , Nakamori T , Watanabe T
Published: December 2015

1. Intravenous bacterial endotoxin, or endogenous pyrogen, in high concentration both caused biphasic fever in rabbits. In low concentration they produced only the first phase of fever. 2. Subcutaneous indomethacin suppressed the first phase of fever produced by high concentration of intravenous endotoxin or endogenous pyrogen, but not the second phase. 3. Intraventricular cerebral injection of indomethacin reduced the second phase of fever produced by high concentration of intravenous endotoxin or endogenous pyrogen, but not the first phase. 4. Intraventricular cerebral injection of endotoxin or of endogenous pyrogen caused slow monophasic fever. This was suppressed by intraventricular, but not by subcutaneous, indomethacin. 5. It is concluded that the first phase of biphasic fever is caused by pyrogen acting via structures outside the blood‐brain barrier, presumably peripheral nerves, and the second phase by pyrogen acting via structures within the blood‐brain barrier, presumably hypothalamic neurones.
Non‐cholinergic component of rat splanchnic nerves predominates at low neuronal activity and is eliminated by naloxone.
Authors: Malhotra R K , Wakade A R
Published: December 2015

1. Effects of nicotinic (mecamylamine) and muscarinic (atropine) receptor antagonists were investigated on the secretion of catecholamines evoked by stimulation of splanchnic nerve terminals and acetylcholine in the isolated perfused adrenal gland of the rat to determine whether non‐cholinergic substances released from nerve terminals participate in the secretion of catecholamines. 2. Increasing the frequency of stimulation from 0.5 to 10 Hz (300 pulses) caused enhanced secretion of catecholamines (26‐110 ng/collection period). After blockade of nicotinic and muscarinic receptors with mecamylamine and atropine, the secretion was reduced by 40, 65 and 80% at 0.5, 1 and 10 Hz, respectively. Acetylcholine‐evoked secretion of catecholamines, which was roughly equivalent to that produced by stimulation at 10 Hz, was blocked by over 90% by the cholinergic antagonists. 3. Naloxone (3‐300 microM) caused a concentration‐dependent inhibition of catecholamine secretion evoked by stimulation of splanchnic nerves (1 Hz); acetylcholine‐evoked secretion was much less affected by naloxone. 4. The secretion of catecholamines that remained after blockade of cholinergic receptors at different frequencies of stimulation (see 2 above) was almost completely inhibited by inclusion of 30 microM‐naloxone in the medium. The inhibitory effect of naloxone was concentration dependent (3‐30 microM) and reversible. 5. Splanchnic nerve‐evoked secretion of catecholamines was facilitated by 400% in the presence of tetraethylammonium or tetraethylammonium plus mecamylamine and atropine. The facilitatory effect of tetraethylammonium was inversely related to the frequency of stimulation. 6. The residual secretion of catecholamines obtained after blockade of cholinergic receptors was facilitated by increasing concentrations of tetraethylammonium (1‐5 mM). 30 microM‐naloxone antagonized the facilitatory effects of tetraethylammonium at 1 and 3 mM by 60% and 25%, respectively, but failed at 5 mM‐tetraethylammonium; higher concentrations of naloxone (100 microM) were also ineffective. 7. It is concluded that neurally evoked secretion of catecholamines is mediated by acetylcholine and a non‐cholinergic substance(s); the contribution of non‐cholinergic substance(s) predominates at low neuronal activity, whereas that of acetylcholine is maximum at high neuronal activity. Blockade of the non‐cholinergic component by naloxone suggests that an opioid peptide may be involved in the secretion of catecholamines in the rat adrenal medulla.
Acetylcholine metabolism and choline availability at the neuromuscular junction of mature adult and aged rats.
Authors: Smith D O , Weiler M H
Published: December 2015

1. The balance between acetylcholine (ACh) synthesis and degradation and the availability of choline were studied in the neuromuscular junction of rats aged 10 (mature adult) and 28 (aged) months. Endogenous and 2H4‐labelled variants of ACh and choline were assayed during steady‐state stimulated and resting conditions using gas chromatography‐mass spectrometry. 2. Endogenous ACh levels were 34% less per nerve terminal in the older rats; in non‐innervated tissue, the levels were 12‐14% as large as in innervated tissue. Endogenous choline levels in innervated and non‐innervated tissue were similar and were 28% higher in the older animals. 3. Accumulation of 2H4‐labelled choline was significantly greater in the 28‐month animals; the specific activity at equilibrium was 60% higher in the older rats. 4. Incorporation of [2H4]choline into [2H4]ACh was significantly faster in the aged rats; times to half‐maximal values were 2.0 and 0.6 min in the 10‐ and the 28‐month animals, respectively. There was no measurable synthesis of ACh in the non‐innervated tissue. 5. There were no major age‐related differences in the amount of ACh released during stimulation between 1 and 20 Hz. In contrast, choline efflux during stimulation was significantly greater in the aged animals; flux values (+/‐ S.E. of mean) were 0.48 (+/‐ 0.014) and 0.66 (+/‐ 0.038) nmol/min for the 10‐ and the 28‐month rats, respectively. 6. Under resting conditions, endogenous ACh efflux was significantly greater in the older rats; the rates (+/‐ S.E. of mean) were 2.00 (+/‐ 0.21) and 3.05 (+/‐ 0.43) pmol/min for the younger and the older animals, respectively; similarly, choline efflux was greater in the aged tissue. 7. These results indicated that lower intracellular ACh levels can be attributed to enhanced leakage rather than to decreased synthesis. Greater ACh efflux is accompanied by correspondingly greater choline uptake in the 28‐month rats; this is associated with greater choline efflux and higher steady‐state choline levels in the aged tissue.
Characteristics of early‐ and late‐recruited oxytocin bursting cells at the beginning of suckling in rats.
Authors: Moos F , Richard P
Published: December 2015

1. Paired or single recordings of paraventricular and/or supraoptic oxytocin cells at the beginning of suckling in urethane‐anaesthetized rats enabled us to study cell recruitment and compare the characteristics of the early‐ and late‐recruited cells. This was done under different experimental conditions, i.e. when the reflex was triggered in less than 1 h suckling (control), and when its triggering was facilitated either by the intraventricular (i.c.v.) injection of oxytocin, of apomorphine (a dopamine agonist) or by the intravenous (i.v.) injection of propranolol (a beta‐adrenoceptor antagonist) into suckled rats with no milk ejection. 2. Under control conditions, the amplitude (total number of spikes) of the successive bursts of the early‐recruited cells progressively increased, generally reaching maximum by the 6th burst. This increase was more rapid and greater after oxytocin than under control conditions or after apomorphine injection, and was delayed and reduced after propranolol. The burst frequency was higher after oxytocin and apomorphine injections than under control conditions and very low after propranolol. 3. Late‐recruited cells were observed under all experimental conditions, except after oxytocin injection, since all cells displayed bursts right away. Moreover, when injected during the recruitment period of a control reflex, oxytocin greatly speeded up the recruitment of the late‐recruited cells. These cells generally displayed smaller amplitude bursts than the early‐recruited cells. Moreover, the increase in burst amplitude was less marked for the late‐ than for the early‐recruited cells and often was not sustained. 4. Neither the likelihood of recruitment of an oxytocin cell nor its burst amplitude could be correlated with background activity level and there was no clear relationship between the recruitment period or the bursting characteristics on one hand and the background activity on the other. 5. In conclusion, the differences between the early‐ and late‐recruited cells in recruitment time and in burst amplitude reflected differences in cell excitability which may depend mainly on the presence of oxytocin in the magnocellular nuclei.
Gestational changes in the utilization of intracellularly stored calcium in the myometrium of guinea‐pigs.
Authors: Coleman H A , McShane P G , Parkington H C
Published: December 2015

1. The ability of oxytocin and prostaglandin F2 alpha (PGF) to induce contraction in guinea‐pig myometrium in calcium‐free solution was studied in an attempt to assess the extent to which intracellular calcium stores could be released by these two agonists. Both longitudinal and circular muscle layers were studied separately and the effects of gestational age were also examined. 2. In longitudinal strips, the responses to oxytocin and PGF in the absence of external calcium decreased progressively throughout gestation. Responses of circular strips to both agonists were unchanged throughout pregnancy, until day 64, when no response to PGF could be elicited. 3. Pre‐treatment with high potassium (and normal calcium) increased the responses to the agonists in calcium‐free medium while pre‐treatment with beta‐adrenoceptor agonists had no effect on responses to oxytocin or PGF. 4. Responses to both agonists decreased with time in calcium‐free solution suggesting a loss of calcium from stores with a half‐time of 3 min. The rate of the decline in the responses was the same in both muscle layers and did not change with gestational age. 5. In the presence of lanthanum contractions evoked by oxytocin, but not PGF, were augmented 2‐3‐fold. This potentiation of the response to oxytocin occurred in both muscle layers and throughout gestation. 6. Each agonist evoked only one response in calcium‐free solution containing EGTA. The response to PGF in longitudinal strips following a challenge with oxytocin was reduced, compared with the response to PGF when applied first while the response to oxytocin in these strips was unchanged following exposure to PGF. In circular strips neither oxytocin‐ nor PGF‐induced contractions were altered following prior exposure to the other agonist. 7. It is concluded that oxytocin and PGF operate via two distinct mechanisms to release intracellularly stored calcium in both longitudinal and circular components of the guinea‐pig myometrium and a hypothesis to explain the results is presented.
Effects of extracellular calcium concentration and dihydropyridines on contraction in mammalian skeletal muscle.
Authors: Dulhunty A F , Gage P W
Published: December 2015

1. Twitches, tetanic contractions and potassium contractures were recorded isometrically from small bundles of rat soleus muscle fibres. 2. Solutions with reduced calcium concentrations (low‐calcium solutions), whether buffered with EGTA (85 and 3 microM‐Ca2+) or not (15 microM‐Ca2+), caused an initial potentiation of contraction followed by depression. 3. The decay of potassium contractures (200 mM‐potassium) was more rapid than normal in low‐calcium solutions. 4. Recovery from the inactivation produced by a 200 mM‐potassium contracture was slowed in low‐calcium solutions but full recovery was seen within 10‐15 min after return to a solution containing 2.5 mM‐Ca2+. 5. Nifedipine (50 microM) in solutions containing 2.5 mM‐Ca2+ potentiated contraction whereas, in low‐calcium solutions, contraction was depressed and the depression was more pronounced the lower the Ca2+ concentration. 6. As with low‐calcium solutions, potassium contractures decayed more rapidly in solutions containing nifedipine. Nifedipine slowed still further the rate of recovery from inactivation in low‐calcium solutions. 7. (‐) Bay K 8644 (50 microM) depressed contraction, increased the rate of decay of potassium contractures and slowed recovery from inactivation, like nifedipine. The racemate of Bay K 8644 was less effective. 8. In explanation of these and other observations, it is proposed that there is a dihydropyridine‐binding molecule in the walls of the transverse tubular system that normally exists predominantly in a 'precursor' form at the resting membrane potential and is converted by membrane depolarization to an 'activator' form essential for excitation‐contraction coupling. Conversion of the precursor to activator involves both conformational change and dissociation of calcium. Prolonged depolarization converts activator to an inactivated form by inducing further conformational change and dissociation of calcium. Recovery from inactivation requires reverse conformational changes and rebinding of calcium. The dihydropyridines affect contraction by reducing the affinity of the molecule for calcium.
Voltage‐gated sodium and potassium currents and their variation in calcitonin‐secreting cells of the chick.
Authors: Kawa K
Published: December 2015

1. The electrical properties of dissociated ultimobranchial cells from chick embryos (18‐20 days after fertilization) were studied using whole‐cell patch electrodes. Antibodies for immunohistological identification of calcitonin‐secreting cells in the preparation were obtained by immunizing rabbits with a conjugated analogue of eel calcitonin. 2. In a proportion of cells, spike‐like action potentials were generated in response to depolarization when cells were immersed in standard saline containing 140 mM‐Na+ but no Ca2+. When the membrane potential was shifted from a holding potential (‐83 ‐ ‐103 mV) to a test depolarization (‐50 mV or more positive) under voltage‐clamp conditions, a transient inward current was produced which was followed by a slowly developing outward current. 3. The inward current was identified as a Na+‐carried current, since (1) the kinetics of the current seemed fast and the amplitude consistently depended on the holding potential, (2) replacement of external Na+ with choline ions reversibly abolished the current, and (3) external application of tetrodotoxin (1 microM) abolished the current completely. The cells in which inward currents were detected showed intense to intermediate degrees of staining with anti‐calcitonin antibodies. 4. In some other cells, no regenerative potentials were evoked even with intense depolarization, but a delayed decrease in membrane depolarization during the current pulse was observed. Voltage‐clamp experiments in these cells revealed the existence of slowly developing outward currents, and the cells showed an intermediate degree of antibody staining. 5. The outward currents in both types of cells were selectively diminished in the presence of K+ channel blockers such as tetraethylammonium (1‐10 mM) or 4‐aminopyridine (1 mM). When the pipette contained 120 mM‐CsCl, none of the dissociated cells exhibited any appreciable outward currents. Thus, the outward currents were most likely to be membrane potential‐dependent K+ currents. The potential dependency of activation and inactivation of the currents were consistent with those of delayed K+ rectifier. 6. In the remaining cells, only passive responses of membrane potentials were observed with current injection. No discernible voltage‐dependent inward or outward currents were detected under voltage‐clamp conditions. Although these cells had a similar appearance to the two types of cells previously mentioned under phase‐contrast microscopy, none of them showed significant antibody staining. These cells were presumed to represent non‐secretory or supporting cells within the gland.(ABSTRACT TRUNCATED AT 400 WORDS)
Cl‐ ‐ and K+‐dependent inhibitory postsynaptic potentials evoked by interneurones of the rat lateral geniculate nucleus.
Authors: Crunelli V , Haby M , Jassik‐Gerschenfeld D , Leresche N , Pirchio M
Published: December 2015

1. Hyperpolarizing potentials evoked by electrical stimulation of the optic tract were studied in projection cells of the rat dorsal lateral geniculate nucleus (LGN) in vitro. In the same cells the effects of gamma‐amino butyric acid (GABA), baclofen and acetylcholine (ACh) were also investigated. 2. In the majority of cells a short‐ (SHP) (34 ms) and a long‐lasting (LHP) (240 ms) hyperpolarizing potential could be recorded in the presence and in the absence of a preceding EPSP. They were blocked by tetrodotoxin (1 microM) and were more sensitive than the monosynaptic EPSP to a low‐Ca2+‐high‐Mg2+ solution. 3. The SHP was associated with a marked decrease (75%) in input resistance, was blocked by bicuculline (1‐100 microM) and its reversal potential (‐67 mV) was dependent on the extracellular Cl‐ concentration. 4. The LHP was associated with a smaller decrease (45%) in input resistance and its reversal potential (‐76 mV) was dependent on the extracellular K+ concentration. It was increased by bicuculline (100% at 50 microM) and nipecotic acid (30% at 10 microM), blocked by Ba2+ (1 mM), and unaffected by eserine (1‐10 microM), neostigmine (1‐10 microM) or by recording with EGTA‐filled electrodes. In the presence of bicuculline, a single LHP was able to evoke, as a rebound response, a low‐threshold Ca2+ spike that was, however, not followed by another LHP (or any other long‐lasting hyperpolarization). 5. Ionophoretic applications of GABA evoked in the same cell a Cl‐ ‐dependent hyperpolarization (reversal potential: ‐65 mV) and/or depolarization, both of which were associated with a marked decrease (91%) in input resistance and abolished by bicuculline. GABA was also able to evoke a bicuculline‐insensitive, K+‐dependent hyperpolarization that had a reversal potential of ‐75 mV and was associated with a smaller decrease (43%) in input resistance. 6. Baclofen, applied by ionophoresis, pressure ejection or in the perfusion medium (1‐100 microM), produced a hyperpolarization that had a reversal potential of ‐79 mV and was associated with a decrease (45%) in input resistance. 7. In the majority of cells (thirty‐seven out of forty) ACh evoked a slow depolarization and only in three cells a hyperpolarization which had a reversal potential of ‐80 mV.(ABSTRACT TRUNCATED AT 400 WORDS)
N‐methyl‐D‐aspartate‐activated channels of mouse central neurones in magnesium‐free solutions.
Authors: Ascher P , Bregestovski P , Nowak L
Published: December 2015

1. The whole‐cell and outside‐out configurations of the patch‐clamp method were used to investigate the properties of the channels activated by N‐methyl‐D‐aspartate (NMDA channels) in mouse central neurones in culture. Recording was made in Mg2+‐free solutions. 2. In the whole‐cell recording mode the currents induced by both NMDA and L‐glutamate were accompanied by a large increase in noise. In both cases the noise power spectra were well fitted by single Lorentzian functions and the corresponding mean time constant, tau, was about 6 ms at room temperature. The single‐channel conductance, gamma n, estimated from the ratio of the noise variance to the total current, varied between 22 and 40 pS. 3. Endogenous amino acids known to activate NMDA receptors (L‐glutamate, L‐aspartate, L‐cysteine sulphinate and quinolinate) as well as exogenous NMDA agonists such as ibotenate and trans‐2,3‐piperidine dicarboxylate (trans‐PDA) all produced similar responses. In particular, analysis of the current noise yielded tau values between 4 and 8 ms in all cases. 4. NMDA responses were antagonized by 2‐amino‐5‐phosphonovalerate (APV) without any effect on gamma n or tau values measured by noise analysis; NMDA responses were also diminished by D‐alpha‐aminoadipate and cis‐2,3‐piperidine dicarboxylate. 5. In outside‐out patches, it was observed that the single‐channel current amplitude varies linearly as a function of membrane potential between ‐80 and +60 mV. The reversal potential is near 0 mV. NMDA channels are permeable to Na+, K+ and Cs+, but blocked by choline. The single‐channel conductance, gamma e, varies between 40 and 50 pS at room temperature. 6. The NMDA channels open in bursts of short openings interrupted by brief closures. At ‐60 mV, the closures had a mean duration, tc, of 0.4 +/‐ 0.2 ms. The mean channel open time, to, was 5.9 +/‐ 1.0 ms for NMDA and 5.3 +/‐ 1.7 ms for L‐glutamate. The mean burst duration, tb, was 10.5 +/‐ 0.7 ms for NMDA and 8.5 +/‐ 2.0 ms for L‐glutamate. 7. When the temperature was increased between 14 and 24 degrees C, the NMDA channel conductance increased with a Q10 of 1.6 while the mean open time decreased with a Q10 close to 2. 8. The NMDA channel showed, in addition to the 'main' conductance state (40‐50 pS), smaller conductance states of 15 and 35 pS.(ABSTRACT TRUNCATED AT 400 WORDS)
The directional sensitivity of the photoreceptors in the human achromat.
Authors: Nordby K , Sharpe L T
Published: December 2015

1. The anatomical nature of the retinal photoreceptors in a typical, complete achromat was investigated by measuring their directional sensitivity. 2. A small (0.5 deg), brief (94 ms) test flash was placed at threshold by varying either its intensity (indirect method) or the intensity of a large (5 deg) adapting field (direct method). The dependent variable was the intensity of light required for the detection threshold as a function of the position of entry in the pupil. An infra‐red viewing system was used to monitor the achromat's pupil and eye position. 3. At both scotopic and mesopic adapting field luminances, the complete achromat's receptors displayed only a small directional sensitivity effect. The effect was not wavelength dependent and could be attributed solely to the rods. 4. The results are consistent with other psychophysical evidence indicating that the complete achromat's retinae lack the post‐receptoral function of the cone photoreceptors. Therefore they do not confirm previous reports that complete achromats have a second, high‐intensity type of photoreceptor.
In vivo permeability of the human placenta to inulin and mannitol.
Authors: Bain M D , Copas D K , Landon M J , Stacey T E
Published: December 2015

1. Permeability of the term human placenta to inulin and mannitol was measured in six normal pregnancies. 2. Bolus and continuous infusion of inulin and mannitol to the mother for 1‐2 h before delivery by Caesarean section achieved steady‐state maternal serum concentrations. Net accumulation of inulin and mannitol in the fetus was measured by the subsequent neonatal urinary excretion. 3. Transplacental clearance was calculated by dividing the net flux by the time‐averaged transplacental concentration gradient. Clearance for inulin was 0.86 +/‐ 0.1 ml min‐1 (mean +/‐ S.E.M.) and for mannitol 7.3 +/‐ 0.8 ml min‐1 (n = 6 in both cases).
In vitro effects of substance P on neonatal rat sympathetic preganglionic neurones.
Authors: Dun N J , Mo N
Published: December 2015

1. Intracellular recordings were made from antidromically identified sympathetic preganglionic neurones (SPNs) in thin transverse neonatal rat thoracolumbar spinal cord slices. 2. Applied either by pressure ejection or superfusion, substance P (SP) caused a slow, monophasic depolarization in 60% of sympathetic preganglionic neurones; a biphasic response consisting of an initial hyperpolarization followed by a depolarization was observed in a few neurones. In addition, SP induced the occurrence of repetitive inhibitory postsynaptic potentials (IPSPs) in about 20% SPNs. 3. Low‐Ca2+ or tetrodotoxin (TTX)‐containing Krebs solution abolished the hyperpolarizing phase of the biphasic response and the small IPSPs, thereby augmenting the depolarizing response of SP. 4. SP‐induced depolarizations were often associated with a moderate increase in membrane resistance. Generally, the response was made smaller on hyperpolarization and reversed at the membrane potential between ‐90 and ‐100 mV. These findings suggest that a reduction of membrane K+ conductance may underlie the depolarizing action of SP. 5. Subthreshold fast, excitatory postsynaptic potentials (EPSPs) evoked by stimulation of dorsal rootlets were consistently augmented during SP‐induced depolarization, leading to cell discharge. 6. Focal stimulations elicited, in addition to a fast EPSP, a slow EPSP in about 40% of SPNs. The slow EPSP was often associated with an increased membrane resistance and became smaller on hyperpolarization. 7. In 15% of SPNs that generated a slow EPSP, the latter was reversibly abolished during SP‐induced depolarization; the blockade persisted when the membrane potential was restored to the resting level by hyperpolarizing current. 8. It is concluded that SP is excitatory to SPNs and that its synaptic release may initiate a slow EPSP which serves to augment impulse transmission through SPNs. Further, it appears that inhibitory interneurones may also be sensitive to SP and their activation may provide a negative feed‐back mechanism which can limit excessive excitation of SPNs by the peptide.
Antinociceptive actions of descending dopaminergic tracts on cat and rat dorsal horn somatosensory neurones.
Authors: Fleetwood-Walker S M , Hope P J , Mitchell R
Published: December 2015

1. The actions of dopamine (DA) and DA receptor specific agonists and antagonist ionophoretically applied in the spinal dorsal horn, and of focal electrical stimulation in the region of the supraspinal DA cell groups (A9 and A11) were assessed on the somatosensory responses of dorsal horn neurones, in both the rat and cat. The neurones tested were multireceptive, giving reproducible responses to both noxious (using a mechanical pinch or radiant heat) and innocuous (using a motorized brush) cutaneous stimuli, as well as to ionophoretically applied DL‐homocysteic acid (DLH, a direct excitant). In the cat, all neurones tested were identified as belonging to the spinocervical tract (SCT) and were located in the dorsal horn laminae III‐V, whilst in the rat, spinothalamic tract (STT) and spinomesencephalic (SMT) neurones located in the region of lamina I and laminae III‐V were tested. 2. Ionophoretically applied DA and RU24213, a D2 DA receptor agonist, caused a selective inhibition of the responses to noxious stimuli of SCT, STT and SMT neurones, whilst the responses to non‐nociceptive stimuli, spontaneous activity and DLH‐evoked activity were unaffected. This action was reversed in the presence of sulpiride, the highly selective D2 DA receptor antagonist. Neither sulpiride alone nor SKF38393, a D1 DA receptor agonist, altered evoked or spontaneous activity when ionophoretically applied. 3. Focal electrical stimulation in the region of the A11, but not the A9, DA cell group selectively suppressed nociceptive responses of spinal, multireceptive neurones in the rat. This stimulus‐evoked effect was consistently and rapidly reversed by ionophoresis of sulpiride, in the vicinity of the dorsal horn neurone being tested. In contrast, naloxone and idazoxan (RX781094), an alpha 2‐antagonist, were not effective. 4. This study presents data supporting a selective antinociceptive role for DA at the spinal level, where it has a widespread antinociceptive influence, on cells in both the superficial and deeper dorsal horn. The A11 DA cell group was shown to be a supraspinal site from which a selective antinociceptive action could be electrically evoked and which was mediated by DA at the level of the dorsal horn.
Hypothalamic inhibition of neurones in the nucleus tractus solitarius of the cat is GABA mediated.
Authors: Jordan D , Mifflin S W , Spyer K M
Published: December 2015

1. In pentobarbitone‐anaesthetized cats extracellular activity of neurones in the vicinity of the nucleus tractus solitarius receiving inputs from the carotid sinus nerve (SN) and/or vagus nerve (VN) during stimulation of the hypothalamic defence area (HDA) and application of gamma‐aminobutyric acid (GABA) and glycine and their antagonists have been studied. 2. A total of forty neurones have been tested, of which twenty‐four only had an input from the SN, one only from the VN, twelve from both nerves and three had neither SN or VN inputs. 3. Short trains of stimuli to the HDA inhibited both the ongoing activity (if present) and evoked discharge in thirty‐nine of the forty neurones tested. 4. In the forty cells tested ionophoretic application of GABA reduced (4) or totally inhibited (35) neuronal discharge whilst in the thirty‐eight tested with glycine discharge was totally (25) or partially (12) suppressed. 5. Ionophoresis of bicuculline totally (14) or partially (6) antagonized the inhibitory actions of GABA in the twenty‐five cells tested, and in eighteen of these the ongoing and/or evoked activity was simultaneously increased. In eighteen of the nineteen cells tested this level of bicuculline also antagonized the inhibitory actions of HDA stimuli whereas in none of the sixteen cells tested did it affect glycine‐evoked inhibitions. 6. Ionophoretic application of strychnine antagonized the inhibitory effects of glycine in eight of nine cells tested but in these eight cells strychnine had no effect on ongoing or evoked discharges, GABA‐ or HDA‐evoked inhibitions. 7. In a chloralose‐anaesthetized cat five neurones receiving SN inputs (three also receiving VN inputs) were recorded. All could be inhibited by HDA stimuli and by application of GABA. In the three of four cells in which bicuculline antagonized GABA inhibitions, the effects of HDA stimuli were simultaneously antagonized whereas glycine‐evoked inhibitions were unaffected. 8. In two neurones, in addition to inhibiting neuronal discharge HDA stimulation also evoked activity in the cells. In a further four neurones similar excitatory responses were uncovered when the HDA inhibitory effects were antagonized by bicuculline. 9. The importance of these observations in cardiovascular control and in the functioning of the baroreceptor reflex is discussed.
Saturation of calcium channels in single isolated smooth muscle cells of guinea‐pig taenia caeci.
Authors: Ganitkevich VYa  , Shuba M F , Smirnov S V
Published: December 2015

1. Calcium channel currents were recorded in Cs+‐dialysed voltage‐clamped single smooth muscle cells isolated from the guinea‐pig taenia caeci to evaluate the current‐carrying ability of Ca2+, Ba2+, Sr2+ and Mg2+ ions. 2. Ba2+ and Sr2+ ions, as well as Ca2+ ions, were able to carry an inward current through calcium channels. Calcium channel current was not observed when Mg2+ was the only divalent cation in the external solution. 3. Concentration dependences of calcium (ICa), barium (IBa) and strontium (ISr) currents were studied. It was found that currents through calcium channels saturated with increasing the extracellular concentration of a current carrier. Saturation of each current can be fitted with a Langmuir curve with apparent dissociation constants of 1.2 mM for Ca2+, 1.8 mM for Sr2+ and 9.6 mM for Ba2+ ions. 4. External Mg2+ ions reduced both ICa and IBa.IBa was depressed to a greater extent than ICa by Mg2+ ions. Reduction of ICa by Mg2+ ions seems to agree with competitive antagonism between Ca2+ and Mg2+ ions (Hagiwara & Takahashi, 1967). 5. When the external divalent cation concentration [( C2+]o) was changed, the current‐voltage relationship of currents through calcium channels was shifted along the potential axis suggesting that activation gating of calcium channels was affected by [C2+]o. These voltage shifts can be fitted with the Gouy‐Chapman theory supposing the density of surface charges near calcium channels to be 0.5 e nm‐2 and including more potent binding of Ca2+ ions to surface charges than of Ba2+, Sr2+ and Mg2+ ions. 6. The changes in the Ca2+, Ba2+ and Sr2+ concentrations at the surface of the membrane were calculated. It was found that saturation of IBa can be explained by saturation of Ba2+ surface concentration while saturation of ICa and ISr cannot. 7. It was suggested that barium ions were able to carry the larger current through calcium channels in smooth muscle cells due to their much weaker binding within the calcium channel.
Depression of mechanical function due to active shortening in the chick anterior latissimus dorsi muscle.
Authors: Becker P L , Murphy R A
Published: December 2015

1. The depressive effect of shortening on the mechanical properties of the chick anterior latissimus dorsi muscle was assessed by the isovelocity method during tetanic stimulation where the muscle was subjected to a standard conditioning shortening (7% optimum length at approximately 2% maximum shortening velocity, V0) immediately prior to the isovelocity test. Comparison was made to the mechanical properties of non‐conditioned (control) contractions. For any given test isovelocity shortening rate, the observed force was always lower if it was preceded by a conditioning shortening. The percentage difference in isovelocity force between conditioned and control contractions was independent of the test shortening velocity. This suggests that shortening lowered the peak isometric force (F0), but did not affect the shape of the force‐velocity relation if normalized to a lower F0. 2. Velocity of unloaded shortening, independently measured by the 'slack' method, was unaffected by the conditioning shortening. 3. The magnitude of the force deficit was diminished if the velocity of the conditioning shortening was increased. 4. Recovery of the force deficit was evaluated by allowing a variable period of isometric force redevelopment between the end of the conditioning shortening and the onset of the test isovelocity shortening. The isovelocity force of the conditioned contraction was less than the corresponding control at all times. Complete recovery was not observed with up to 5 s of additional stimulation. However, recovery was observed if the muscle was allowed to relax briefly. 5. Several possible interpretations of our results were considered. Our results are consistent with the hypothesis that the effect of shortening results from non‐uniform sarcomere shortening due to a pre‐existing heterogeneity of sarcomere strengths. 6. An Appendix describes: (1) how the force‐velocity relation would be affected due to the presence of sarcomere strength heterogeneity, and (2) how a model muscle consisting of a heterogeneous population of sarcomeres would be expected to behave following different types of shortenings.
The effect of heart rate on the membrane currents of isolated sheep Purkinje fibres.
Authors: Boyett M R , Fedida D
Published: December 2015

1. The effect of the rate of stimulation on the membrane currents of sheep Purkinje fibres at 37 degrees C has been examined. 2. In the diastolic range of potentials, the pacemaker current if was unchanged at different stimulus rates. 3. On going from 6 to 60 min‐1 the effect on the background current was similar to that of a decrease in the bathing K+ concentration, because there was a decrease in outward current in the plateau range of potentials and an increase in outward current in the diastolic range of potentials. At rates above 60 min‐1 there was extra outward background current at all potentials. Partial block of the Na+‐K+ pump by ouabain reduced these changes in background current. 4. On going from 6 to 60 min‐1 there was an increase in the slow inward current isi, but at rates above 60 min‐1 there was usually a decrease in isi. The decrease in isi at rates greater than 60 min‐1 was in part the result of insufficient time between action potentials for complete recovery of isi from inactivation. 5. The effect of these rate‐dependent changes in membrane current on electrical activity has been considered. 6. The increase in the pacemaker potential at high rates is likely to be the consequence of the decrease in membrane conductance at diastolic potentials as a result of the changes in background current. 7. The increase in the maximum diastolic potential at high rates is likely to be the result of the extra outward background current at diastolic potentials. 8. The prolongation of the action potential on going from 6 to 60 min‐1 is likely to be the result of the increase of isi, as well as the decrease in outward background current at plateau potentials. 9. The shortening of the action potential above 60 min‐1 is likely to be the result of the decrease in isi although the extra outward background current may also contribute.
Characterization of voltage‐gated sodium channels in ovine gonadotrophs: relationship to hormone secretion.
Authors: Mason W T , Sikdar S K
Published: December 2015

1. The properties of whole‐cell Na+ currents (INa) were studied in immunocytochemically identified ovine gonadotrophs using the patch clamp technique. 2. Voltage recording under current clamp revealed that gonadotrophs did not fire spontaneously, and fired only a single action potential in response to a depolarizing current clamp step. 3. Under voltage clamp, INa was found to be sensitive to tetrodotoxin (TTX) and had an activation threshold of about ‐75 mV, with peak current occurring at ‐20 to ‐30 mV. 4. Using a two‐pulse protocol a delay in the onset of inactivation was observed, suggesting that inactivation is dependent on and preceded by the activation phenomenon. 5. Kinetics of recovery from inactivation of the Na+ channels were studied with test pulses applied at various times after a depolarizing pre‐pulse. Recovery from inactivation showed an initial delay, in contrast to the predictions of the Hodgkin‐Huxley equations. 6. Recovery from inactivation was examined by using a repetitive pulse protocol, showing approximately 1 s is required for the channels to achieve a 95% recovery. 7. The steady‐state inactivation (h infinity ‐V) curve was sigmoidal and fitted by a logistic growth curve model. The half‐inactivation value of the Na+ current occurred at a membrane potential of ‐70 +/‐ 8 mV. 8. Noise power spectra derived from fluctuations of INa could be fitted with a single Lorentzian function, and the time constant value was slower at more depolarizing potentials. 9. The single‐Na+‐channel conductance was estimated from fluctuation analysis under conditions of reduced Na+ current amplitude by depolarizing pre‐pulses. The single‐channel conductance derived by the above method (approximately equal to 11 pS) corresponded to the single‐channel conductance derived from single‐channel current measurements using the outside‐out version of the patch clamp technique (approximately equal to 13 pS). 10. Inactivation of INa was slowed by including 15 mM‐iodate in the pipette. Ensemble fluctuation analysis of INa under these conditions was carried out using the steady state portion of the inactivation phase of the modified INa records, revealing a process best fitted by a double Lorentzian power spectrum, consistent with inactivation kinetics involving both a fast and a slow process. The time constant values correlated well with those obtained from a double‐exponential fit to the decaying inactivation phase of the iodate‐modified INa.(ABSTRACT TRUNCATED AT 400 WORDS)
Modulation of calcium channel currents in guinea‐pig single ventricular heart cells by the dihydropyridine Bay K 8644.
Authors: Markwardt F , Nilius B
Published: December 2015

1. A single glass micropipette voltage clamp technique with intracellular dialysis was used to study Ba2+ currents in isolated ventricular cells from guinea‐pig hearts. Effects of the 1,4‐dihydropyridine Bay K 8644 on whole‐cell currents were evaluated at 37 degrees C. 2. Bay K 8644 increased the Ba2+ peak currents at test potentials between ‐50 and +20 mV and shifted the current‐voltage relationships towards hyperpolarizing potentials (leftward shift for Ca2+ channel activation, 13.8 +/‐ 4.1 mV; n = 9; Bay K 8644, 5 mumol/l). 3. The peak times of the Ba2+ currents were diminished over the voltage range tested between ‐40 and +20 mV after Bay K 8644 in parallel with a shortening of the time constant of activation that was estimated from fits of the recorded currents with a d2f model. 4. The decay of the Ba2+ currents was fitted with two exponentials including a pedestal. The compound Bay K 8644 accelerated the fast decay over the whole voltage range. The amplitude of the rapidly inactivated component of the Ba2+ currents was strikingly increased after application of Bay K 8644. 5. The steady‐state inactivation using a 0.5 or 5 s pre‐pulse was shifted towards hyperpolarizing potentials (leftward shift 10.3 +/‐ 5.2 mV; n = 4; Bay K 8644, 5 mumol/l). 6. The change in the time course of Bay K 8644‐modified Ba2+ currents cannot be described solely by a decrease of the backward rate coefficient from an open to a closed state of the Ca2+ channel (Sanguinetti, Krafte & Kass, 1986). The described effects of Bay K 8644 on the inactivation can be both qualitatively and quantitatively described by a model of current‐dependent inactivation (Standen & Stanfield, 1982), assuming a lower affinity of an internal binding site for Ba2+ than for Ca2+.
Removal of periaxonal potassium accumulation in a squid giant axon by outward osmotic water flow.
Authors: Kukita F
Published: December 2015

1. Periaxonal potassium accumulation does not occur in a squid giant axon when outward water flow is maintained by an osmotic gradient across the axolemma. Potassium concentrations in the periaxonal space were calculated from the potassium potentials (EK) for the tail K+ current. With outward water flow, the periaxonal K+ concentration was maintained at values less than or close to the K+ concentration in the bathing solution. 2. Outward osmotic water flow was produced by adding 1 M‐urea to the isotonic external solution. This was sufficient to prevent K+ accumulation, but it had no effect if applied to both sides of the axolemma. 3. The thickness of the periaxonal space (theta s) and the permeability of the extracellular barrier (Ps) were estimated using a three‐compartment model. Under isotonic conditions they were 25 nm and 3.7 micron/s, respectively. With outward water flow, either Ps or theta s or both must increase by a large factor, since K+ accumulation is prevented. 4. Instantaneous I‐V relations with outward water flow showed outward rectification and no time‐dependent changes in their shape. When external K+ concentration was increased, the curves became more linear.
Improving the spatial resolution of epiretinal implants by increasing stimulus pulse duration
Authors: Weitz Andrew C. , Nanduri Devyani , Behrend Matthew R. , Gonzalez-Calle Alejandra , Greenberg Robert J. , Humayun Mark S. , Chow Robert H. , Weiland James D.
Published: December 2015

Retinal implants that deliver longer pulses of electrical current may markedly improve image sharpness for blind individuals.
Therapeutic targeting of casein kinase 1δ in breast cancer
Authors: Rosenberg Laura H. , Lafitte Marie , Quereda Victor , Grant Wayne , Chen Weimin , Bibian Mathieu , Noguchi Yoshihiko , Fallahi Mohammad , Yang Chunying , Chang Jenny C. , Roush William R. , Cleveland John L. , Duckett Derek R.
Published: December 2015

Casein kinase 1δ promotes breast tumorigenesis by activation of β-catenin and can be targeted in some breast cancers.
Comment on “Dengue virus NS1 protein activates cells via Toll-like receptor 4 and disrupts endothelial cell monolayer integrity” and “Dengue virus NS1 triggers endothelial permeability and vascular leak that is prevented by NS1 vaccination”
Authors: Halstead Scott B.
Published: December 2015

New insights into toxicity of dengue virus protein NS1 provide context to previous work and prompt further questions.
Response to comment on “Dengue virus NS1 protein activates cells via Toll-like receptor 4 and disrupts endothelial cell monolayer integrity” and “Dengue virus NS1 triggers endothelial permeability and vascular leak that is prevented by NS1 vaccination”
Authors: Stacey Katryn J. , Watterson Daniel , Modhiran Naphak , Young Paul R.
Published: December 2015

Multiple risk factors may cause progression to severe dengue.
AD and CAA: Independent risk factors for dementia
Authors: Janson Christopher G.
Published: December 2015

Cerebral amyloid angiopathy, a neurovascular disease of the elderly, is highly prevalent in patients with Alzheimer's disease and is associated independently with dementia.