bluuebunny/crossref_metadata_2025 huggingface dataset:
Submandibular responses to stimulation of the sympathetic innervation following parasympathetic denervation in cats.
Authors: Edwards A V , Garrett J R
Published: December 2014

1. The effects of continuous stimulation of the ascending cervical sympathetic nerve were compared with those of intermittent stimulation in bursts, so arranged as to deliver the same total number of impulses, in cats under chloralose anaesthesia 3 weeks after excision of the chorda tympani. 2. Parasympathetic denervation of the gland in this way enhanced the vasodilator component of the vascular response during sympathetic stimulation in bursts. During continuous stimulation this was manifested as a reduced rise in submandibular vascular resistance (SVR). It also produced a profound increase in the secretory response to sympathetic stimulation at low intensity (2 Hz continuously). 3. Enhancement of the salivary secretory responses by stimulating intermittently at relatively high frequencies resembled that which developed following parasympathetic denervation in that there was no change in the secretory capacity during maximal or supramaximal stimulation. 4. Pre‐treatment with atropine substantially reduced the flow of saliva in response to sympathetic stimulation at low frequencies (2 and 5 Hz continuously) and combined pre‐treatment with atropine and propranolol effectively reversed the increase in secretory sensitivity due to parasympathetic denervation indicating that beta‐adrenergic and muscarinic responses are involved. Additional pre‐treatment with dihydroergotamine effectively abolished the secretory response to sympathetic stimulation. 5. Stimulation in bursts was found to have a significantly greater vasodilator effect than continuous stimulation at the corresponding frequency after parasympathetic denervation. 6. Neither pre‐treatment with atropine nor combined pre‐treatment with atropine and propranolol had any significant effect on the changes in mean SVR at any frequency tested during or after either pattern of stimulation. Additional pretreatment with dihydroergotamine effectively abolished the vascular responses to sympathetic stimulation both continuous (5 Hz) and in bursts (50 Hz), leaving a small vasoconstrictor response that may be due to release of neuropeptide Y (NPY). 7. These results suggest that cholinergic beta‐adrenergic and NPY supersensitivities are not involved in the submandibular vascular changes that result from parasympathetic denervation, but that alpha‐mediated secondary vasodilator mechanisms are thereby enhanced.
Relaxation and hyperpolarization of the smooth muscle of the rat tail artery following electrical stimulation.
Authors: Kotecha N , Neild T O
Published: December 2014

1. The smooth muscle of the rat tail artery was made to constrict with noradrenaline or 5‐hydroxytryptamine. Electrical stimulation of the contracted artery caused a transient hyperpolarization and relaxation. 2. The hyperpolarization and relaxation could be recorded from denervated arteries, showing that these responses were independent of the perivascular nerves. 3. Removal of the vascular endothelium caused only a small reduction in the relaxation. 4. Raising the external K+ concentration to 20 mM abolished or greatly reduced the relaxation, and caused some reduction of the hyperpolarization. 5. 1 mM‐tetraethylammonium chloride abolished both the hyperpolarization and the relaxation. 6. From the membrane potential‐contraction relationship for this artery it appeared that the hyperpolarization could account for some but not all of the relaxation.
Nutrient uptake by rat enterocytes during diabetes mellitus; evidence for an increased sodium electrochemical gradient.
Authors: Debnam E S , Karasov W H , Thompson C S
Published: December 2014

1. The effect of streptozotocin‐induced diabetes (7 day duration) in rats on D‐glucose uptake in vivo, the unidirectional uptake of D‐glucose and L‐proline in vitro, the passive uptake of L‐glucose in vitro and the potential difference across the brush‐border membrane has been studied. 2. Diabetes resulted in an increased carrier‐mediated glucose uptake both in vivo and in vitro and a stimulation of L‐proline uptake at a concentration of the amino acid (0.025 mM) at which uptake was largely Na+ dependent. Diabetes was without effect on uptake using a proline concentration of 50 mM at which transport was predominantly Na+ independent. 3. A marked hyperpolarization of the brush‐border membrane and an enhanced passive glucose uptake were also evident during diabetes. 4. We conclude that the stimulation of glucose uptake in vivo in diabetic intestine involves events at the brush‐border membrane. The mechanisms include an increased surface area for uptake and an enhanced transmembrane electrical gradient. The latter will have a major effect on the transport of other substrates when the uptake pathway is primarily Na+ dependent.
Transient inward current in guinea‐pig atrial myocytes reflects a change of sodium‐calcium exchange current.
Authors: Lipp P , Pott L
Published: December 2014

1. Enzymatically isolated, cultured myocytes from hearts of adult guinea‐pigs were voltage clamped with a whole‐cell patch‐clamp technique. The pipette‐filling solution for internal dialysis contained 65 mM‐citrate and 50 microM‐EGTA as Ca2+‐chelating agents and 20 mM‐Na+. Potassium channel currents were blocked by replacing this ion on both sides of the membrane by Cs+. 2. In the above conditions myocytes develop spontaneous transient inward currents (Iti) at constant negative membrane holding potentials. At a given membrane potential Iti can be recorded with constant amplitude and frequency for periods of up to ca. 40 min. A membrane current with similar properties can be evoked by superfusion of the cell with caffeine‐containing (5‐10 mM) solution. 3. Depolarization results in a reduction of Iti amplitude and a prolongation of its duration. After a step change of the membrane potential to ca. ‐10 mV or a less‐negative level only one inward current change is observed. Thereafter the membrane current remains inward with regard to the instantaneous current at this membrane potential. Complete relaxation of Iti then is only observed after repolarization to a more‐negative membrane potential. 4. The current change caused by sarcoplasmic Ca2+ release is inward in a range of membrane potentials between ‐90 and +75 mV. A reversal of Iti was never detected. 5. Both the instantaneous current‐voltage (I‐V) relation and voltage dependence of peak Iti display distinct outward rectification. Both I‐V relations can be described by a formalism suggested for a membrane current caused by electrogenic Na+‐Ca2+ exchange (INa, Ca) assuming a 3:1 stoichiometry and a single energy barrier in the electric field of the membrane. 6. An increase of the time integral of Iti at the holding potential is observed after depolarizations to positive membrane potentials, where the outward‐rectifying current component is prominent. This supports the view that the outward current represents INa, Ca in the 'reverse mode', carrying Ca2+ ions into the cell. 7. After prolonged cell dialysis a run‐down of Iti is observed. Since strong depolarizations in this condition still can cause inward currents upon repolarization, run‐down is likely to reflect an impairment of sarcoplasmic reticulum function rather than an effect of cell dialysis on the exchanger. 8. We conclude that under the present conditions a membrane current is measured, which to a large extent determines the 'passive' I‐V curve of the myocytes. This current is modified by a rise in Ca2+(i) following sarcoplasmic Ca2+ release.(ABSTRACT TRUNCATED AT 400 WORDS)
Changes in hypothalamic temperature modulate the neuronal response of the ventral thalamus to skin warming in rats.
Authors: Morimoto A , Murakami N , Sakata Y
Published: December 2014

1. The influence of hypothalamic temperature on the activity of warm‐excited neurones, which responded to skin warming with an increased firing rate, in the ventro‐basal (VB) complex of the thalamus of rats was examined electrophysiologically. 2. The warm‐excited neurones were classified into three types: hypothalamus‐cold neurones in which the firing rate increased with hypothalamic cooling, hypothalamus‐warm neurones in which the firing rate increased with hypothalamic warming and hypothalamus‐insensitive neurones in which the firing rate was not affected by hypothalamic temperature. The majority of hypothalamus‐cold and hypothalamus‐warm neurones increased their firing rate at hypothalamic temperature below and above 38 degrees C, respectively. 3. The threshold temperature at which hypothalamus‐warm neurones responded to skin warming was lowered by hypothalamic warming. However, hypothalamus‐cold neurones responded to lower skin temperatures during hypothalamic cooling. 4. These results show that the neuronal activity of the VB complex in the thalamus, responding to skin warming, is affected by hypothalamic temperature. Thus thermal information from the peripheral thermoreceptors is modulated by hypothalamic temperature at the level of the relay nuclei of the thalamus.
Presynaptic effects of d‐tubocurarine on neurotransmitter release at the neuromuscular junction of the frog.
Authors: Matzner H , Parnas H , Parnas I
Published: December 2014

1. Presynaptic effects of d‐tubocurarine on neurotransmitter release were examined at the frog neuromuscular junction, using intracellular and extracellular recording techniques. 2. d‐Tubocurarine in concentrations of 10(‐7)‐10(‐6) M decreased the quantal content (m) measured by the coefficient of variation and failure methods. 3. d‐Tubocurarine produced a shift to the right of the curve relating log quantal content to log [Ca2+]o without changing the slope. 4. The duration of twin‐impulse facilitation was not affected by 5 x 10(‐7) M‐d‐tubocurarine. Early facilitation was higher in d‐tubocurarine. 5. d‐Tubocurarine altered the synaptic delay histogram. The peak of the histogram was shifted to longer delays. Prolongation of the minimal delay was seen in most but not all experiments. 6. These results suggest that d‐tubocurarine inhibits release of neurotransmitter by affecting a stage in the process of release, which occurs after the entry of Ca2+ ions.
Changes in the surface pH of voltage‐clamped snail neurones apparently caused by H+ fluxes through a channel.
Authors: Thomas R C
Published: December 2014

1. The surface and intracellular pH of snail neurones was recorded with microelectrodes while the membrane potential was reduced in 10 mV steps for a few seconds each or to positive values for periods of several minutes. 2. Depolarizations to positive membrane potentials caused rapid falls in surface pH (pHs) which varied from cell to cell and from one point to another on the surface of the same cell. 3. When pHi was normal or alkaline, the first few 10 mV steps of depolarization often caused a small pHs increase which changed to a decrease as the depolarization increased. The threshold potential at which the pHs increase changed to a decrease varied with pHi in a linear manner, so that at acid pHi values the threshold potential approached the normal resting potential. There was good agreement between the threshold and H+ equilibrium potentials calculated from pHi and pHs. 4. The size of the pHs decrease observed at a given pHi and depolarization depended on extracellular buffering power in a non‐linear manner. Solutions buffered with 20 mM‐NaHCO3 had similar surface buffering power to CO2‐free solutions buffered with only 1‐2 mM‐HEPES, pH 7.5. 5. In 1 mM‐HEPES pHs changes were larger, and pHi increases slower, than those seen in cells depolarized to the same potential in 20 mM‐HEPES. The slowing of the rate of pHi increase suggests that the pHs changes occur all over the cell surface, and not only at the recording site. 6. With long‐lasting depolarizations the size of the pHs decrease was proportional to the rate of pHi increase and thus, assuming a constant intracellular buffering power, to the rate of efflux of H+. 7. The results provide further evidence that snail neurones possess a channel permeable to H+ which is opened on depolarization. H+ efflux through this channel could cause rapid acidification of a confined extracellular space.
The effect of stimulation of the atrial receptors on plasma renin activity in the dog.
Authors: Drinkhill M J , Hicks M N , Mary D A , Pearson M J
Published: December 2014

1. To determine whether stimulation of atrial receptors reflexly results in a consistent change in plasma renin activity experiments were performed in dogs anaesthetized with alpha‐chloralose. Either a large balloon in the lumen of the left atrium or small balloons positioned at the upper and middle pulmonary vein‐atrial junctions and atrial appendage were distended. Plasma samples obtained from these dogs during control periods and during periods of stimulation were assayed for plasma renin activity. 2. In the first series of experiments, stimulation of left atrial receptors by either large or small balloon distension was shown to result in an increase in urine flow and a decrease in plasma renin activity. 3. In a second series of experiments, cooling of the cervical vagosympathetic nerve trunks abolished the response of an increase to balloon distension in urine flow and decrease in plasma renin activity. 4. It was shown that a decrease in plasma renin activity resulted in response to stimulation of atrial receptors, and that this decrease is reflex in nature and is likely to involve only atrial receptors discharging into myelinated vagal fibres.
The influence of pH on membrane conductance and intercellular resistance in the rat lens.
Authors: Bassnett S , Duncan G
Published: December 2014

1. The conductance of the rat lens was measured using a two‐internal‐microelectrode technique. The voltage response to a step of current consisted of two components arising from bulk and membrane resistance respectively. 2. The potassium permeability was calculated by applying Goldman theory to 86Rb+ efflux data. 3. The internal pH (pHi) and internal free calcium (pCai) were measured directly using single‐ and double‐barrelled ion‐sensitive microelectrodes. 4. Lens pHi was 6.9 in control solution (external pH, pHo = 7.3) and was reduced on lowering pHo. The presence of propionate or 100% CO2 in the external solution accentuated this effect. 5. Internal acidification was accompanied by a depolarization of membrane potential, an increase in membrane and cell‐to‐cell resistance and a decrease in potassium permeability. The acidification had no effect on pCai. 6. The intracellular pH was increased by perifusing with trimethylamine or NH4Cl. Both treatments induced a membrane depolarization with little change in potassium permeability. Subsequent removal of NH4Cl led to a sustained decrease in pHi. 7. In every case where pHi decreased, the changes in membrane potential and conductance could be explained largely on the basis of a decrease in potassium permeability. The concomitant increase in cell‐to‐cell resistance was less pronounced and probably insufficient to uncouple the lens system.
Direct observations of effects of baroreceptor stimulation on mesenteric circulation of the rat.
Authors: Hébert M T , Marshall J M
Published: December 2014

1. In anaesthetized rats, supramaximal baroreceptor stimulation by carotid sinus inflation evoked a reflex fall in systemic arterial pressure and an increase in gross mesenteric vascular conductance, but no significant change in gross mesenteric blood flow. 2. Principal arteries (80‐350 microns internal diameter (i.d.)) which supply the intestine and mesentery, small arteries (30‐40 microns) and some terminal arterioles (18‐30 microns) of the mesentery showed a diameter increase beginning with the fall in arterial pressure, but remaining terminal arterioles and precapillary arterioles (10‐18 microns) showed a diameter increase beginning when arterial pressure neared its lowest level. 3. Application of phentolamine to the mesentery abolished diameter increases that began with the reflex fall in arterial pressure. Thereafter, 50% of small arteries and terminal and precapillary arterioles showed diameter increases that began when the fall in arterial pressure neared its zenith. 4. It is proposed that the proximal arterial vessels, which are known to be sympathetically innervated, predominantly showed dilatation mediated by reflex inhibition of sympathetic tone, while more distal arterioles showed myogenic dilatation secondary to the fall in systemic arterial pressure. 5. Small veins (30‐50 microns) of the mesentery and principal veins (100‐560 microns) that drain mesentery and intestine also showed a diameter increase beginning with the reflex fall in systemic arterial pressure. Since they are known to have a sympathetic noradrenergic supply, and in the absence of changes in mesenteric blood flow likely to cause passive changes in venous diameter, they apparently showed dilatation due to inhibition of sympathetic tone. 6. The above responses are all compatible with, and so suggest underlying mechanisms for, changes in blood flow, regional blood volume, and capillary filtration evoked by baroreceptor stimulation in studies of whole mesenteric circulation, i.e. intestine as well as mesentery.
Vascular changes during penile erection in the dog.
Authors: Carati C J , Creed K E , Keogh E J
Published: December 2014

1. The vascular effects of pelvic nerve stimulation on the penis were studied in dogs anaesthetized with sodium pentobarbitone and halothane. Changes in pressure and blood flow were measured through scalp vein needles inserted into the erectile bodies. 2. The penis contains two types of erectile body, which responded independently during erection induced by pelvic nerve stimulation. Pressure in the corpus spongiosum increased immediately upon stimulation, but only reached one‐third of the more delayed pressure response of the corpora cavernosa. 3. At rest, arterial inflow resistance into the corpora cavernosa was high, whereas venous outflow resistance was low. Pelvic nerve stimulation (10‐50 V, 10‐16 Hz, 1 ms) caused an immediate increase in arterial flow, an increase in corpus cavernosal pressure (CCP), and a decrease in venous outflow. Saline infusion experiments showed there was active venous occlusion. Upon cessation of stimulation, these parameters returned to pre‐stimulation levels. 4. The time taken to reach 50% of maximum change in arterial inflow was significantly less than for CCP, which was significantly less than for venous outflow. Occlusion of the aorta 1 min after cessation of stimulation decreased the pressure in the arterial tree supplying the corpora cavernosa, but CCP remained elevated, indicating that both inflow and outflow resistances were high. Thus, inflow resistance had returned to its pre‐stimulation state before outflow resistance. 5. Direct measurements of blood flow through the corpus cavernosum were made with a hydrogen probe. There was a transient increase in blood inflow as CCP increased during pelvic nerve stimulation. There was some blood flow while CCP was elevated, indicating that the venous occlusion was not complete. 6. Sympathetic chain stimulation caused an increase in arterial resistance, and a decrease in CCP and venous resistance. 7. Infusions of acetylcholine (330 micrograms min‐1) and vasoactive intestinal polypeptide (1‐3.3 micrograms min‐1) decreased arterial resistance and increased CCP and venous resistance. 8. This study suggests that during pelvic nerve‐induced erection, arterial flow into the corpus cavernosum increases, followed by an increase in CCP and an actively controlled decrease in venous outflow.(ABSTRACT TRUNCATED AT 400 WORDS)
Site and mechanism of activation of proton‐induced sodium current in chick dorsal root ganglion neurones.
Authors: Davies N W , Lux H D , Morad M
Published: December 2014

1. In dissociated and cultured 1‐ to 2‐day‐old chick dorsal root ganglion cells, and in isolated outside‐out membrane patches, a large transient current lasting 1‐2 s could be activated upon step increases in [H+]o. The proton‐induced current reversed direction at the Na+ equilibrium potential, was abolished completely in the absence of Na+, and was therefore labelled INa(H). 2. To investigate the activation and deactivation kinetics of INa(H) at the single‐channel level, we employed isolated membrane patches and a method whereby we could change the external solution in less than 1 ms. 3. In outside‐out membrane patches, INa(H) was fully activated within 2 ms between pH 6.7 and 5.7. Half‐times of activation decreased with increasing [H+]o. The calculated association rate constant was 9.5 x 10(9) M‐1 s‐1. 4. Deactivation of INa(H), following a step reduction in [H+]o, occurred with half‐times of within 1.3‐2 ms. 5. In the continued presence of an activating solution (pH 6.7 and 1 mM‐Ca2+), INa(H) inactivated slowly, with a time constant of about 300 ms. 6. Inactivation showed a limited dependence on [Ca2+]o. The time constant of inactivation increased from about 300‐500 ms as [Ca2+]o was decreased from 5 to 0.1 mM. Further decrease in [Ca2+]o did not significantly increase the time course of inactivation. Increases in [Ca2+]i from 10(‐9) to 10(‐3) M had no effect on the activation or inactivation kinetics of INa(H). 7. Conditioning proton concentrations which by themselves failed to activate any channel openings, partially inactivated INa(H). 8. Recovery from inactivation appeared to follow a time course similar to that of inactivation itself. 9. INa(H) could not be activated in inside‐out patches. A step increase in proton concentration outside a cell‐attached patch was also ineffective at producing INa(H) in the patch. Intracellular pH between 7.9 and 6.7 had no effect on the activation or inactivation of INa(H). 10. The activation and inactivation kinetics were not significantly voltage dependent. 11. The single‐channel conductance associated with the activation of INa(H) was 28 pS in symmetrical 120 mM‐NaCl solutions and remained constant throughout the time course of INa(H). 12. During activation of the voltage‐gated calcium current, ICa, a step increase in proton concentration caused a rapid (ca. 2 ms) suppression of ICa which was more than that predicted from the steady‐state effects of H+ on ICa. This effect was independent of [Na+] and the direction of INa(H).(ABSTRACT TRUNCATED AT 400 WORDS)
Evidence for co‐transport of sodium, potassium and chloride in mouse pancreatic islets.
Authors: Lindström P , Norlund L , Sandstöm P E , Sehlin J
Published: December 2014

1. The presence of a loop diuretic‐sensitive co‐transport system for Na+, K+ and Cl‐ was tested in isolated pancreatic islets. 2. Substitution of Cl‐ with the impermeant anion isethionate or addition of frusemide both reduced the ouabain‐resistant islets uptake of 86Rb+ (K+ marker) without affecting the ouabain‐sensitive uptake or equilibrium content of 86Rb+. The effects of Cl‐ substitution and frusemide were overlapping. 3. D‐Glucose reduced the ouabain‐resistant islets uptake of 86Rb+. This effect was additive to the effect of Cl‐ substitution or frusemide. 4. Substitution of Cl‐ with isethionate or addition of frusemide both reduced the efflux of 86Rb+ from the islets. These effects were additive to the reduction of 86Rb+ efflux induced by D‐glucose. 5. Substitution of K+ or Na+ with choline reduced the equilibrium content of 36Cl‐ in the pancreatic islets. 6. These data are compatible with the operation in the pancreatic beta‐cells of a loop diuretic‐sensitive co‐transport system for Na+, K+ and Cl‐, that may serve as an inwardly directed Cl‐ pump.
Kinetic analysis of voltage‐ and ion‐dependent conductances in saccular hair cells of the bull‐frog, Rana catesbeiana.
Authors: Hudspeth A J , Lewis R S
Published: December 2014

1. By the use of whole‐cell and excised‐patch tight‐seal recording techniques, we studied ionic conductances in voltage‐clamped solitary hair cells isolated from the bull‐frog's sacculus. As a basis for assessing their contributions to hair cell electrical resonance, we developed kinetic models describing voltage‐dependent Ca2+ and Ca2+‐dependent K+ conductances. 2. A transient K+ current (IA) was activated by steps to potentials positive to ‐50 mV from holding potentials more negative than ‐70 mV. In the steady state, the current was fully inactivated at the normal resting potential. Possibly due to the dissipation of a Donnan potential between the pipette's interior and the cell, the voltage dependence of IA inactivation slowly shifted in the negative direction during whole‐cell recording. 3. The voltage‐gated Ca2+ current (ICa) was isolated by blocking IA with 4‐aminopyridine (4‐AP) and Ca2+‐activated K+ current with tetraethylammonium (TEA). The ICa was activated at potentials more positive than ‐60 to ‐50 mV and was maximal at about ‐10 mV. Its magnitude was highly variable among cells, with an average value of ‐240 pA at ‐30 mV. Its activation could be fitted well by a third‐order (m3) gating scheme. 4. A Ca2+‐activated K+ current (IK(Ca)) was isolated as the component of membrane current blocked by TEA. This current was activated at potentials more positive than ‐60 to ‐50 mV and had an average value of 1.5 nA at ‐30 mV. The Ca2+‐activated K+ conductance (gK(Ca)) showed a high apparent voltage dependence, increasing e‐fold every 3 mV at potentials between ‐50 and ‐40 mV. 5. The Ca2+‐activated K+ current displayed rapid activation and deactivation kinetics. The current reached half‐maximal activation in 2‐4 ms at voltages between ‐50 and ‐30 mV, and the tail current decayed exponentially with a time constant of 1.0 ms at ‐70 mV. The activation rate and magnitude of IK(Ca) were reduced by lowering the extracellular Ca2+ concentration. 6. The open probability of Ca2+‐activated K+ channels was estimated by ensemble‐fluctuation analysis of whole‐cell currents evoked by voltage steps to ‐30 mV. The average open probability was estimated to be 0.8 at this potential. 7. K+‐selective channels with a high conductance (140‐200 pS) were examined in excised, inside‐out membrane patches. The activity of these channels depended on intracellular Ca2+ and membrane potential. These properties suggest that the channels underlie the whole‐cell Ca2+‐activated K+ current.(ABSTRACT TRUNCATED AT 400 WORDS)
A model for electrical resonance and frequency tuning in saccular hair cells of the bull‐frog, Rana catesbeiana.
Authors: Hudspeth A J , Lewis R S
Published: December 2014

1. Electrical resonance in solitary hair cells was examined under several experimental conditions using the tight‐seal recording technique in the whole‐cell current‐clamp mode. 2. Resonance was characterized by the frequency and quality factor of oscillations in membrane potential evoked by depolarizing current pulses. Oscillation frequency increased with depolarization, from about 90 Hz at the resting potential to a limiting value of about 250 Hz. The quality factor of the oscillations was a bell‐shaped function of membrane potential that reached a maximum of up to 12.6 at a potential slightly positive to the resting potential. 3. Pharmacological experiments were performed to assess which of three ionic currents participate in electrical resonance. Reduction of the voltage‐gated Ca2+ current (ICa) and the Ca2+‐activated K+ current (IK(Ca)) by lowering the extracellular Ca2+ concentration, or reduction of IK(Ca) with tetraethylammonium ion (TEA) degraded the resonance. In contrast, blockade of the transient K+ current (IA) with 4‐aminopyridine (4‐AP) had no significant effect. 4. To test the sufficiency of the Ca2+ and the Ca2+‐activated K+ currents to account for resonance, we developed a model using mathematical descriptions of the two currents derived in the preceding paper (Hudspeth & Lewis, 1988), with additional terms for leakage conductance and membrane capacitance. The model correctly predicts the oscillatory responses to applied current pulses, including the non‐linear dependences of oscillation frequency and quality factor on membrane potential. 5. Simulations of current‐clamp experiments in the presence of a reduced extracellular Ca2+ concentration or of TEA were generated respectively by decreasing the model's values for the maximal Ca2+ or Ca2+‐activated K+ conductances. The model's predictions of membrane‐potential oscillations under these conditions agree qualitatively with experimental results, providing further support for the model as a description of the resonance mechanism. 6. To identify the factors most important in determining the hair cell's resonance properties, we systematically altered the values of selected parameters in the model. Frequency was most profoundly influenced by increasing the magnitude and activation rate of the Ca2+‐activated K+ conductance, whereas the quality factor was most sensitive to increases in the level of the Ca2+ conductance. 7. By including a term describing activation of the hair cell's mechanically sensitive transduction conductance, we used the model to predict a tuning curve for responses to mechanical inputs of various frequencies.(ABSTRACT TRUNCATED AT 400 WORDS)
On the mechanism of isoprenaline‐ and forskolin‐induced depolarization of single guinea‐pig ventricular myocytes.
Authors: Egan T M , Noble D , Noble S J , Powell T , Twist V W , Yamaoka K
Published: December 2014

1. Isoprenaline (10 nM to 1 microM) and forskolin (0.6‐100 microM) depolarized single guinea‐pig myocytes studied in vitro. Under voltage clamp both agents caused an inward current to flow. 2. These effects were abolished by propranolol (100 nM) and the beta1‐antagonist metoprolol (100‐200 nM), but not by the beta2‐agonist [corrected] salbutamol (1 microM). 3. The interaction of isoprenaline with forskolin, caffeine or isobutylmethylxanthine (IBMX) on current amplitude was as expected if all of these drugs were causing inward current by increasing intracellular levels of cyclic adenosine monophosphate (cyclic AMP). Low concentrations of forskolin (less than 600 nM) or IBMX (less than 20 microM) potentiated the effect of isoprenaline, whereas isoprenaline caused no further inward current in cells in which high concentrations of forskolin (600 nM‐100 microM) or IBMX (20 microM‐1 mM) were already evoking maximum inward current. 4. Isoprenaline‐induced inward current was reduced 30‐50% by acetylcholine (10‐30 microM). This action of acetylcholine was blocked by atropine (100 nM). 5. The effect of isoprenaline on holding current was critically dependent on temperature. The onset of the current was delayed and its amplitude reduced as the myocyte was cooled from 37 degrees C to ambient temperature (22‐24 degrees C). 6. Isoprenaline‐induced inward current was not affected by the potassium channel blockers barium (2 mM) or tetraethylammonium (TEA; 10‐20 mM). The amplitude of the inward current did not vary as a function of [K+]o. 7. The inward current was not affected by the calcium channel blockers cadmium 1 mM, or nifedipine (10 microM), or when internal calcium was reduced by including EGTA in the recording electrode filling solution. 8. The amplitude of the current was also unaffected by caesium (5 mM), which blocks the hyperpolarization‐activated, non‐specific channel if, or by strophanthidin (10 microM) which blocks the Na+‐K+ pump. It was unchanged by substitution of external chloride by isethionate. 9. The inward current was absent when external sodium was replaced by the impermeant ion tetramethylammonium (TMA). 10. Isoprenaline‐ and forskolin‐induced inward currents were associated with an increase in both membrane chord conductance and noise. The increase in conductance was most readily measured at potentials where the inwardly rectifying potassium channel, iK1, was small, or when iK1 was blocked by the addition of barium (2 mM).(ABSTRACT TRUNCATED AT 400 WORDS)
Receptors in the bill of the platypus.
Authors: Gregory J E , Iggo A , McIntyre A K , Proske U
Published: December 2014

1. Afferent responses were recorded from filaments of the trigeminal nerve in each of two platypuses (Ornithorhynchus anatinus) anaesthetized with alpha‐chloralose. All receptive fields were located along the lateral border of the upper bill. Discrete receptive fields could be identified as belonging to two distinct classes of sensory receptor. 2. The most prominent response was an irregular resting discharge which could be increased or decreased by weak electric pulses. These receptors were insensitive to moderately strong mechanical stimulation, and it was concluded that they were electroreceptors. 3. Each electroreceptor had a single spot of maximum sensitivity on the bill surface. When the stimulating electrode over this spot was the cathode it excited the receptor for the duration of the stimulating pulse, using stimulus strengths as low as 20 mV. When it was the anode, it inhibited the discharge. Cathodal excitation was followed by rebound inhibition and anodal inhibition by rebound excitation. 4. Receptors responded to cathodal steps with an initial high‐frequency burst of impulses, followed by a lower maintained rate of discharge. Rapidly changing pulses were similarly effective in exciting receptors, adding support to the claim that platypuses are able to detect moving prey by the electrical activity associated with muscle contraction. 5. The centres of the receptive fields of two electroreceptors were marked by the insertion of fine entomological pins. Histological examination established the presence of a large mucus‐secreting gland at the marked spot. The epidermal duct of the gland contained an elaborate myelinated innervation, with morphologically distinct axon terminals that we identify as the electroreceptors. 6. As well as electroreceptors, the skin of the bill contained three kinds of mechanoreceptors: slow‐adapting receptors, rapidly adapting, vibration‐sensitive receptors and receptors with an intermediate adaptation rate. The slowly adapting receptors were characterized by their low threshold to mechanical stimuli, irregular discharge and significant dynamic sensitivity. Vibration receptors showed maintained responses to sinusoidal vibration of the skin up to 600 Hz. 7. These experiments confirm an earlier report that the platypus bill is an electrodetector organ. The presence of electroreceptors of a unique structure and supplied by the trigeminal nerve indicates that electroreception has evolved independently in monotremes. This in turn emphasizes that monotremes are a highly evolved group which split off from the main mammalian stem a long time ago.
Spike propagation and conduction failure in the rat neural lobe.
Authors: Dyball R E , Grossmann R , Leng G , Shibuki K
Published: December 2014

1. Single units were recorded from the rat hypothalamo‐neurohypophysial system in vivo to test the hypothesis that action potential conduction failure might contribute to the relative inefficiency of neurohypophysial hormone release at low frequencies of stimulation, and following prolonged stimulation. 2. Recordings were made from the cell bodies of supraoptic neurones which project to the neural lobe of the pituitary. Stimuli applied to the neural lobe evoked antidromic action potentials (in ten of forty cells) at times when the axonal membrane at the site of stimulation should have been refractory following the passage of a spontaneous, orthodromically conducted action potential. This observation suggests that failure of orthodromic action potentials may occur intermittently in the neural lobe. 3. Recordings from single units in the neural lobe showed similar spontaneous patterns of activity to those seen from cell bodies in the supraoptic nucleus. 4. Stimuli applied to the neural stalk evoked orthodromically conducted spikes in these single units: evoked spikes followed stimulation faithfully at 50‐80 Hz for 1 s or at 20 Hz for 1 min. Such stimulation was accompanied by a reduction in spike height and a prolongation of latency. 5. Comparable changes were seen in the latency and amplitude of evoked potentials recorded from the neural lobe with low‐resistance electrodes. 6. Stalk stimulation at 50 Hz for 1 s was accompanied by a reduction in the threshold for initiation of action potentials, suggesting an increase in the excitability of neural lobe axons. 7. We conclude that, during low‐frequency activation, spike failure occurs intermittently in neurohypophysial axons, and that changes in the excitability of the axons during activation at high frequencies may contribute to the facilitation of neurohypophysial hormone release that occurs with increasing frequencies of stimulation.
Some membrane properties of the circular muscle of chicken rectum and its non‐adrenergic non‐cholinergic innervation.
Authors: Komori S , Ohashi H
Published: December 2014

1. Membrane properties and innervation of the circular muscle of chicken rectum were investigated by recording intracellularly electrotonic potentials evoked by passing current, and excitatory and inhibitory junction potentials (EJPs and IJPs) evoked by electrical stimulation of the extrinsic or intrinsic nerves. 2. The membrane potential was ‐55 +/‐ 0.6 mV (n = 95). Action potentials of long duration (1.2‐4.0 s) discharged spontaneously, or were generated when the membrane depolarization due to either electrotonic potential or EJP reached the threshold. The drug D600 blocked the generation of action potentials. 3. Electrotonic potentials spread fairly well in the longitudinal direction of the muscle fibres but not in the transverse direction. The longitudinal space constant was 1.7 +/‐ 0.2 mm (n = 10) and the membrane time constant was 205 +/‐ 21 ms (n = 10). 4. Field stimulation of intramural nerves evoked an EJP followed by a long‐lasting IJP (3‐12 s in total duration) in most cells, and an EJP alone or an IJP alone in a small number of cells. The EJP and IJP were preserved in the simultaneous presence of atropine and guanethidine, but abolished with tetrodotoxin. 5. Stimulation of Remak's nerve trunk or its branches produced EJPs which were atropine resistant and guanethidine resistant just like the EJP elicited by intramural nerve stimulation. The extrinsic nerve stimulation was ineffective in eliciting IJPs. 6. The EJP amplitude declined in a linear manner as the distance from the stimulating site of intramural nerves was increased. The decline was much greater along the transverse axis than the longitudinal axis of circular muscle fibres. 7. The reversal potential for the EJP was estimated by extrapolation to be about ‐ 15.3 +/‐ 0.3 mV (n = 7). 8. Apamin did not inhibit the IJP. During the hyperpolarization of a single IJP or summed IJPs, electrotonic potentials remained unchanged or slightly decreased in amplitude.
Reduced voluntary electromyographic activity after fatiguing stimulation of human muscle.
Authors: Garland S J , Garner S H , McComas A J
Published: December 2014

1. After ischaemic ankle dorsiflexor muscles had been fatigued by repetitive stimulation of the peroneal nerve at 15 Hz, there was a reduction in voluntary EMG activity which persisted as long as the arterial cuff remained inflated. 2. The reduction in voluntary EMG activity could not have been due to loss of excitability at the neuromuscular junctions or muscle fibre membranes since the M‐waves (muscle compound action potentials) evoked by peroneal nerve stimulation were well maintained. 3. The preceding observations were consistent with the view that the reduction in EMG activity was due to reflex inhibition of motoneurones by afferents from the fatigued muscle. 4. The absence of responses to stimuli interpolated among the voluntary activity indicated that any motor units which could not be recruited in the fatigued muscle were no longer capable of generating tension.
Quantal secretion at release sites of nerve terminals in toad (Bufo marinus) muscle during formation of topographical maps.
Authors: Bennett M R , Lavidis N A
Published: December 2014

1. The number of quanta secreted from selected sites along terminal branches at suppressed synapses in the developing toad (Bufo marinus) gluteus muscle has been determined. The topographical projection from segmental nerves 8 and 9 to the ventral surface of this muscle matures slowly as toads develop in size from 12 to 40 g. Terminal branches of nerves 8 and 9 were visualized by prior staining with the fluorescent dye, 3‐3‐diethyloxardicarbocyanine iodide (DiOC2(5]. 2. The evoked quantal release recorded with an extracellular electrode (m(e) at different positions along the length of terminal branches at synaptic sites innervated either by nerve 8 (me,8) or nerve 9 (me,9) was determined in an external Ca2+ concentration, [Ca2+]o, of 0.35‐0.45 mM. For over 90% of branches longer than 80 microns, me declined along exponential curves from a relatively large value at the proximal end of branches for both nerve 8 and nerve 9 terminals; the exponent for these exponential curves gave quantal length constants that varied from 26 to 80 microns (48 +/‐ 4 microns, mean +/‐ S.E.M.) depending on the length of the branch. 3. The evoked quantal release recorded with an intracellular electrode (m) at synaptic sites dually innervated by nerve 8 and nerve 9 was nearly always (greater than 90%) greater for nerve 8 terminals than for nerve 9 terminals. At singly innervated sites the value of m per 100 microns length of terminal declined approximately exponentially with an increase in total terminal length (length constant 400 microns). However, at dually innervated sites the value of m per 100 microns length of nerve 9 terminal was very low at all total terminal lengths compared with singly innervated sites; this indicates that nerve 9 terminals were suppressed at dually innervated sites. 4. At five dually innervated sites, seven out of nine terminal branches of nerve 8 showed an exponential decline in me,8 along their length, from a relatively large value near the proximal end of the branches (length constant 35 +/‐ 3 microns, mean +/‐ S.E.M.). In contrast, all the terminal branches of nerve 9 greater than 80 microns showed a uniformly low value of me,9 along their length. 5. It is suggested that the suppression of nerve 9 terminals at dually innervated sites is primarily due to a decrease in the probability of secretion of normally highly secreting release sites at the proximal end of terminal branches.
Post‐natal disappearance of transient calcium channels in mouse skeletal muscle: effects of denervation and culture.
Authors: Gonoi T , Hasegawa S
Published: December 2014

1. The whole‐cell voltage clamp technique was used to record Ba2+ currents in voltage‐sensitive Ca2+ channels in mouse flexor digitorum brevis muscles developing in situ from day 1 to 30 after birth. Effects of denervation and tissue culture on the Ca2+ channel currents were also studied. 2. The muscle fibres in newborn mice showed two distinct types of Ca2+ channel currents, a low‐threshold transient current and a high‐threshold sustained current. 3. The specific amplitude of the transient current was 2.7 +/‐ 1.7 (S.D.) A/F in response to ‐30 mV test pulses in medium containing 30 mM‐Ba2+ on day 1 after birth. The transient current decreased progressively in the post‐natal days and became undetectable by day 17. In contrast, the specific amplitude of the sustained current in response to +20 mV test pulses increased 4‐fold from 6.9 A/F on day 1 to 27.7 A/F on day 30. 4. The disappearance of the transient current could not be accounted for by either shifts in voltage dependence of activation and inactivation or changes in activation and inactivation times of the two types of current during development. 5. Denervating muscle fibres on day 8 after birth did not prevent the disappearance of the transient current. Denervating them on day 17 did not allow reappearance of the transient current. However, the increase of the sustained current was suppressed by the denervation either on day 8 or day 17. 6. In muscle fibres isolated on day 8 after birth and cultured thereafter, the transient current did not disappear until day 19 in culture (27 days after birth), while the sustained current was maintained at the level on day 8. 7. In muscle fibres isolated on day 17, when the transient current had become undetectable, and cultured thereafter, the transient current did not reappear until day 15 in culture (32 days after birth), while the sustained current was maintained at a level similar to that on day 17. 8. We conclude that innervation has little influence on the developmental disappearance of the transient Ca2+ channel current in mouse muscle fibres, and suggest that some influencing factors from surroundings other than the nerve may be required for the disappearance of the functional transient channels.
Properties of the voltage‐dependent calcium channel of mouse Swiss 3T3 fibroblasts.
Authors: Peres A , Sturani E , Zippel R
Published: December 2014

1. Suspended Swiss 3T3 fibroblasts were voltage clamped using the whole‐cell technique. 2. Passage from the cell‐attached to the whole‐cell mode was accompanied by only a minor decrease in input resistance. Direct measurement of resting potential gave values between O and ‐15 mV. 3. In order to account for the effects of leak on the membrane potential measurements, I‐V curves were obtained immediately before and after patch rupture by applying voltage ramps. After subtraction of the cell‐attached current from the whole‐cell current, the true membrane potential was estimated as the zero‐current potential in the I‐V curve. An average value of ‐8.2 +/‐ 0.9 mV in 8 mM‐Ca2+ was obtained in this way. 4. In 2 mM‐Ca2+, step depolarizations 100 ms long from holding potentials (Vh) more negative than ‐60 mV caused a transient inward current to appear. From Vh greater than ‐60 mV only a linear leakage component was apparent. 5. In 2 mM‐Ca2+ depolarizations to potentials greater than +40 mV (from Vh = ‐100 mV) generated transient, outwardly directed currents. 6. Increasing extracellular Ca2+ up to 32 mM shifted the peak current vs. voltage curve and the reversal potential (Erev) towards more positive potentials, and caused an increase of the peak current. 7. The steady‐state inactivation curve was the same for both inward and outward currents, indicating that they flow through the same channels. The currents are completely inactivated at V = ‐60 mV. 8. Recovery of the fully inactivated current upon hyperpolarization had an exponential time course with tau = 0.22 s at V = ‐80 mV and tau = 0.18 s at V = ‐100 mV. 9. In the absence of Ca2+ (but with Mg2+ present) the inward current disappeared but a large, inactivating outward current appeared when V greater than 0 mV. The current was strongly reduced by Cd2+ (1 mM) or Co2+ (10 mM). 10. Complete removal of divalent cations from the external solution caused the channel to become highly permeable to monovalent cations. 11. Nitrendipine (10 microM) and verapamil (5 microM) were unable to block the current. 12. On the whole the present results indicate that voltage‐dependent Ca2+ channels are present in these cells. Their sensitivity to divalent cations, to organic blockers and to potential is similar to that of the low‐voltage‐activated, or ‘T’ type, Ca2+ channels described in other cells.