bluuebunny/crossref_metadata_2025 huggingface dataset:
The regulation of disynaptic reciprocal Ia inhibition during co‐contraction of antagonistic muscles in man.
Authors: Nielsen J , Kagamihara Y
Published: December 2014

1. The disynaptic reciprocal inhibition from ankle dorsiflexors to ankle plantarflexors was investigated at rest, during tonic plantar‐ and dorsiflexion and during co‐contraction. In relation to rest, it was found to be decreased during plantarflexion and co‐contraction, but unchanged during dorsiflexion. 2. When increasing the strength of plantarflexion the amount of inhibition became progressively smaller. Already during weak co‐contraction, the amount of inhibition was very small and it did not become smaller during stronger contraction. The decrease of inhibition during co‐contraction could not be explained by an addition of the changes of inhibition observed during plantar‐ and dorsiflexion individually. 3. The disynaptic reciprocal inhibition was also found to be decreased when the peripheral feedback from the muscles was blocked by inducing ischaemia in the leg and at the beginning of a dynamic co‐contraction before sensory feedback could interfere. This implies that the observed decrease is caused by a central inhibition of the transmission in the pathway. 4. The amount of disynaptic reciprocal inhibition was also investigated during standing. No significant difference in the amount of inhibition was found when the subjects were standing up at rest as compared to sitting down at rest. When the subjects were forced to make a co‐contraction in order to maintain balance, i.e. when they were standing on one leg, leaning backwards or standing on an unstable platform, a decrease of disynaptic reciprocal inhibition was seen. When the subjects leaned forward, thus forcing a contraction of the soleus muscle, a decrease was also seen, but it was smaller than in the co‐contraction tasks. Finally, when the subjects lifted the examined leg, thus contracting the tibialis anterior muscle, either no change or a small increase of inhibition was seen. 5. A similar control of the disynaptic reciprocal inhibition as described for the pathway from ankle dorsiflexors to ankle plantarflexors was also observed for the pathway from ankle plantarflexors to dorsiflexors and from wrist extensors to wrist flexors. 6. It is concluded that when co‐contraction is used in order to stabilize a joint, i.e. to maintain posture, a specific co‐contraction motor programme is activated that depresses the transmission in the disynaptic reciprocal pathway thereby ensuring a high excitability level in the motoneurones of both antagonistic muscles.
Effect of colcemid on the water permeability response to vasopressin in isolated perfused rabbit collecting tubules.
Authors: Phillips M E , Taylor A
Published: December 2014

1. The effect of the microtubule‐disruptive agent, colcemid (N‐deacetyl‐N‐methyl‐colchicine), on the water permeability response to vasopressin has been investigated in isolated cortical collecting tubules from the rabbit kidney perfused in vitro. 2. Pretreatment of collecting tubules with colcemid inhibited the increase in water permeability elicited by vasopressin, 50 microU ml‐1, in a time‐ and dose‐dependent manner. After 75 min exposure to the drug, inhibition of the response to the hormone averaged 72 +/‐ 6% (n = 4, P < 0.01) at a colcemid concentration of 7.2 x 10(‐5) M. Inhibition was estimated to be half‐maximal at a colcemid concentration of 1.9 x 10(‐6) M. 3. Colcemid, 2.7 x 10(‐7) to 7.2 x 10(‐5) M, had no effect on basal water permeability nor on the increase in lumen negative potential difference (PD) induced by the hormone. 4. Lumicolcemid, an isomer of colcemid that does not disrupt microtubules, had no influence on the water permeability response to vasopressin. 5. Pretreatment with colcemid, 2.7 x 10(‐5) M, for 45 min inhibited the water permeability response to 8‐CPT‐cAMP, 1.8 x 10(‐5) M, by 38 +/‐ 4% (n = 5, P < 0.01). 6. When collecting tubules were exposed to colcemid, 5.5 x 10(‐5) M, for 45 min after the hydrosmotic response to vasopressin had been established, the drug had no influence on the maintenance of the raised water permeability. 7. The results provide further evidence that cytoplasmic microtubules play a role in the initiation of the hydrosmotic response to vasopressin in the mammalian collecting tubule at a site distal to the generation of cyclic AMP.
Some properties of Ca(2+)‐induced Ca2+ release mechanism in single visceral smooth muscle cell of the guinea‐pig.
Authors: Zholos A V , Baidan L V , Shuba M F
Published: December 2014

1. Late transient outward Ca(2+)‐dependent K+ current (ILTO) correlated with Ca(2+)‐induced Ca2+ release mechanism was studied in relation to the calcium inward current (ICa) in single isolated smooth muscle cells of the guinea‐pig ileum using the whole‐cell patch‐clamp technique. 2. The voltage dependencies of peak ICa and ILTO were both bell shaped. However, the I‐V curve of the outward current was shifted toward more positive potentials by about 60 mV in comparison to that for ICa. 3. Reduction in the external Ca2+ concentration resulted in a decrease of peak amplitude of both ICa and ILTO. However, caffeine‐induced outward current was also decreased abruptly suggesting a rapid loss of stored Ca2+ upon lowering the external Ca2+ concentration. 4. Investigation of the relation of ILTO to partially inactivated ICa showed that inactivation of ICa by approximately 65, 80 or 84% of control (produced by prepulse to ‐20 mV for 2 s, shifting the holding potential to ‐20 mV for 30 s or by the ramp voltage command from ‐50 to +10 mV, respectively) was without detectable effect on the ILTO generation. 5. Bath application of the Ca2+ antagonist nifedipine (300 nM) inhibited ICa by 81% without affecting ILTO peak amplitude (92.0 +/‐ 5.6% of control in six cells). The mean concentration‐response curve for ICa inhibition was sigmoidal with the apparent dissociation constant of 86.9 nM, whereas that for the ILTO had a characteristic sharp transition indicating a definite threshold of Ca2+ influx for ILTO generation. 6. Application of Ca(2+)‐free external solution during 500 ms of the time when ICa peaked inhibited the current by about 76% whereas the ILTO during such an intervention remained virtually unchanged. 7. In double‐pulse experiments, with conditioning and test pulses to +10 mV from ‐50 mV and an interpulse interval of 600 ms, most of the cells (about 80%) showed larger outward current at the test pulse suggesting continued Ca2+ release triggered by Ca2+ influx during a short (50‐200 ms) depolarizing prepulse. The outward current could also be evoked at large positive potentials (presumably near the calcium equilibrium potential) where it did not occur normally by a prepulse to +10 mV for 50 ms. The charge transferred by Ca2+ current necessary to activate Ca2+ release in most of the cells was estimated to be from 6 to 20 pC. 8. The data are interpreted to suggest that the Ca(2+)‐induced Ca2+ release mechanism operates in single ileal cells in a regenerative manner.(ABSTRACT TRUNCATED AT 400 WORDS)
Alteration of ventilatory activity by intralaryngeal CO2 in the cat.
Authors: Bartlett D , Knuth S L , Leiter J C
Published: December 2014

1. We investigated the responses of phrenic and hypoglossal nerve activities to the addition of 3, 5 and 10% CO2 to a constant flow of warm, humidified air through the isolated upper airway in decerebrate, paralysed, artificially ventilated cats. 2. In bilaterally vagotomized animals, intralaryngeal CO2 caused a dose‐related decrease in peak integrated phrenic activity. This response became attenuated with time, but was still discernible after 3 min of continuous intralaryngeal CO2. In the same experiments, intralaryngeal CO2 caused a gradual increase in peak integrated hypoglossal nerve activity. 3. Intermittent pulsing of intralaryngeal CO2 during neural inspiration or expiration resulted in similar, but smaller decreases in the phrenic activity of some animals. Hypoglossal activity was not influenced appreciably by this procedure. 4. Systemic hypercapnia attenuated the phrenic responses to intralaryngeal CO2. The hypoglossal responses were greatly reduced or abolished. 5. In vagally intact cats, ventilated by a servo‐respirator in accordance with phrenic nerve activity, intralaryngeal CO2 resulted in only a trace of reduction in phrenic discharge. After bilateral vagotomy, the same animals showed typical responses, as described above. 6. All responses to intralaryngeal CO2 were abolished after bilateral section of the superior laryngeal nerves (SLNs). 7. We conclude that intralaryngeal CO2 acts by way of receptors with afferents in the SLNs to decrease phrenic and increase hypoglossal nerve activities. The responses are not importantly gated during neural inspiration or expiration. The responses to intralaryngeal CO2 are most clearly demonstrable after bilateral vagotomy, suggesting that vagal mechanisms serve to stabilize respiratory motor neural activity in intact animals.
Studies of transepithelial Cl‐ transport in cultured cauda epididymal cells of rats by the short‐circuit current method.
Authors: Leung A Y , Wong P Y
Published: December 2014

1. Monolayer cultures of cauda epididymides from male Sprague‐Dawley rats (210‐230 g) were studied by the short‐circuit current (ISC) technique to characterize the properties of the transepithelial chloride transport. In HCO(3‐)‐free, HEPES‐buffered solution, adrenaline (0.23 microM) added to the basolateral side led to an increase in ISC and transepithelial conductance (gt). 2. Decreasing apical chloride concentration ([Cl‐]a) progressively from 126.7 to 0 mM by substituting chloride with gluconate increased the ISC response to adrenaline (delta ISC) in a linear fashion with a slope of ‐1.6 x 10(‐3) mu equiv h‐1 cm‐2 per millimolar change in [Cl‐]a. Pretreating the tissue with a chloride channel blocker diphenylamine‐2‐carboxylate (DPC) on the apical side significantly reduced the slope to ‐4.9 x 10(‐4) mu equiv h‐1 cm‐2 per millimolar change in [Cl‐]a. 3. By substituting apical chloride with various anions and measuring the change in ISC upon adrenaline stimulation, the selectivity sequence of the apical anion conductance was found to be NO3‐ approximately Br‐ > Cl‐ > I‐ > gluconate > isethionate. 4. When the monolayers were bathed with Krebs‐Henseleit solution containing 25 mM HCO3‐ and 5% CO2, the delta ISC at each [Cl‐]a as well as the dependence of delta ISC on [Cl‐]a (slope = ‐3.3 x 10(‐3) mu equiv h‐1 cm‐2 per millimolar change in [Cl‐]a) were significantly greater than the HCO(3‐)‐free counterpart. Addition of 0.1 mM acetazolamide or 0.5 mM SITS (4‐acetamido‐4'‐isothiocyanatostilbene‐2,2'‐disulphonic acid) to the basolateral side significantly reduced the effects of HCO3‐ and CO2. 5. When the tissues were bathed on both sides with HCO(3‐)‐free, HEPES‐buffered solution and were clamped at various transepithelial potential differences (PDt) from +30 mV (lumen positive) to ‐30 mV (lumen negative), the relationship between the clamping current response to adrenaline (delta ICL) and the PDt applied was linear. Zero clamping current response was found at ‐6 mV. Decreasing [Cl‐]a to 0 mM reduced the dependence of delta ICL on PDt and delta ICL was positive at all PDt tested. The response of the transepithelial conductance to adrenaline (delta gt) did not depend on the PDt applied but was reduced with decreasing apical chloride concentration.(ABSTRACT TRUNCATED AT 400 WORDS)
Modulation of calcium current gating in frog skeletal muscle by conditioning depolarization.
Authors: Feldmeyer D , Melzer W , Pohl B , Zöllner P
Published: December 2014

1. Ca2+ inward currents were measured by voltage clamping cut skeletal muscle fibres of the frog (Rana esculenta) in a double‐Vaseline‐gap system. 2. In order to study the basis of the previously described fast gating mode induced in the Ca2+ inward current by a conditioning depolarization we quantitatively analysed the response to differing features of the conditioning prepulse. 3. The faster activation seen during the second of two depolarizations was confined to the component of the inward current which could be blocked by 5 to 10 microM nifedipine. 4. By applying depolarizing conditioning pulses of gradually increasing length the time course of the transition to the fast gating mode could be determined. 5. Both the transition to the fast gating mode (point 4) caused by a depolarization and the slow inward current activated during the same depolarization showed similar voltage‐dependent kinetics. 6. The kinetic change of the test current appeared to be equal when the same fractional activation was achieved at the end of the conditioning pulse independent of its duration or amplitude. 7. Flash photolysis of nifedipine in the interval between conditioning and test pulse showed that the predepolarization causes a rate‐enhancing effect even though the slow channels were blocked by nifedipine during the conditioning pulse. 8. We conclude that the transition of the calcium channel from its slow to its fast gating mode is determined by the slow voltage‐dependent reaction which limits the rate of channel opening under control conditions. This reaction is apparently not prevented by the binding of nifedipine and the block of current flow through the channel.
Different firing patterns generated in dendrites and somata of CA1 pyramidal neurones in guinea‐pig hippocampus.
Authors: Wong R K , Stewart M
Published: December 2014

1. Intracellular recordings, taken from CA1 pyramidal cells in guinea‐pig hippocampal slices, were used to examine the origins of repetitive and burst firing in these cells. Single action potentials were elicited by depolarizing current injection at somatic recording sites. In contrast, current injection during intradendritic recordings initiated burst firing in the dendrites. Burst firing could be elicited in the soma by direct depolarization of distal apical dendrites (> 150 microns from the cell body layer) with large extracellular polarizing electrodes. 2. Intracellular recordings were taken simultaneously from the apical dendrites and pyramidal cell somata with the intention of impaling the same neurone with both electrodes. Paired dendrite‐soma recordings confirmed that rhythmic single action potentials were generated at the cell soma, whereas bursts of action potentials were initiated in the distal apical dendrites (> 150 microns from the cell body layer). Fast spikes in the dendrite often triggered fast spikes in the soma, but not all fast spikes in the dendritic burst were ‘relayed’ to the soma. 3. In paired recordings, when a dendritic action potential failed to elicit a full somatic action potential, a ‘d‐spike’ was commonly recorded in the soma. Somatic d‐spikes were uniform all‐or‐none responses that could be shown, in some cases, to trigger the full somatic action potentials. 4. Attenuated spikes could be recorded in the dendrites, triggered by action potentials initiated at the cell soma. Dendritic responses to somatic stimulation sometimes varied in amplitude, but always showed a direct correspondence with somatic action potentials. 5. Dendritic recordings taken closer to the pyramidal cell bodies (< 150 microns from the cell body layer) showed a ‘transitional’ region where single action potentials rather than burst discharges could be evoked. After‐potentials of these single spikes differed from those associated with somatic spikes in that proximal dendritic spikes had depolarizing after‐potentials. The observed shift from after‐hyperpolarization to depolarizing after‐potentials in intradendritic recordings taken progressively further from the cell body corresponds to the change from repetitive to burst firing. 6. The results indicate that activity of the CA1 pyramidal cell soma, presumably a reflection of its output, can be either burst or repetitive firing. Somatic ‘bursts,’ unlike the burst discharges seen in the apical dendrites or the burst discharges reported in CA3 cells, are not initiated locally. Rather, they appear to be simply a rapid spike‐for‐spike response by the soma to the fast spikes that form part of the apical dendritic burst.(ABSTRACT TRUNCATED AT 400 WORDS)
Contribution of Ca(2+)‐induced Ca2+ release to the [Ca2+]i transients in myocytes from guinea‐pig urinary bladder.
Authors: Ganitkevich V Y , Isenberg G
Published: December 2014

1. Smooth muscle cells from guinea‐pig urinary bladder were studied at an extracellular Ca2+ concentration ([Ca2+]o) of 3.6 mM and 36 degrees C. Fluorescence of Indo‐1 was used to monitor the cytosolic calcium concentration ([Ca2+]i) and its changes ([Ca2+]i transients) induced by step membrane depolarizations. 2. During a 6 s depolarization step from ‐60 to 0 mV [Ca2+]i increased from a resting 118 +/‐ 22 nM to 1150 +/‐ 336 nM and decayed to a sustained level of 295 +/‐ 62 nM. The experiments were designed to evaluate the contribution of the release of intracellularly stored Ca2+ to components of the depolarization‐induced [Ca2+]i transient, i.e. ‘phasic’, which decayed during a maintained depolarization step, and ‘tonic’ which constituted the sustained elevation of [Ca2+]i above resting level. 3. A short (1 s) application of 10 mM caffeine mimicked the phasic component. After wash‐out of caffeine, the subsequent depolarization induced a [Ca2+]i transient with reduced peak, the degree of suppression depending on the interval between wash‐out of caffeine and depolarization. The phasic component of the depolarization and the caffeine‐induced [Ca2+]i transients were not additive but saturative. 4. The phasic component was largely abolished in the continuous presence of 10 mM caffeine. It was also abolished by a 10 min cell dialysis of 10 microM ryanodine from the pipette solution and was strongly reduced by dialysis of 5 microM thapsigargin. Changes of the tonic component of the depolarization‐induced [Ca2+]i transient were much less pronounced with all three interventions. 5. The tonic component of the depolarization‐induced [Ca2+]i transient was increased when [Ca2+]o was elevated briefly before a depolarization close to 0 mV, whereas the phasic component was not significantly changed. Similarly, brief application of 1 microM Bay K 8644 increased the tonic component several‐fold without modifying significantly the phasic component. 6. It is concluded that depolarization‐induced influx of Ca2+ through L‐type Ca2+ channels induces the release of Ca2+ from intracellular caffeine‐sensitive stores which constitutes the major part of the phasic component. Ca2+ release superimposes on the effects of Ca2+ influx through L‐type Ca2+ channels, the non‐inactivating part of which constitutes the tonic component of the [Ca2+]i transient. Since the two processes interact, a dissection by simple subtraction is not possible.
Intracellular calcium dynamics in response to action potentials in bullfrog sympathetic ganglion cells.
Authors: Nohmi M , Hua S Y , Kuba K
Published: December 2014

1. Dynamic changes in the intracellular free Ca2+ concentration ([Ca2+]i) following electrical membrane activity, were recorded from the neurone soma of the excised bullfrog sympathetic ganglion, using Fura‐2 fluorescence and compared with the accompanying Ca(2+)‐dependent electrical membrane responses. 2. The resting [Ca2+]i was about 100 nM, a value little changed by penetration with an intracellular electrode. 3. A net rise in fluorescence at a wavelength of 340 nm (Ca2+ transient) induced by a single action potential in Ringer solution rose almost in parallel with the initial decay phase of a slow Ca(2+)‐dependent after‐hyperpolarization; decayed in parallel with the late phase; and increased in amplitude and duration in the presence of tetraethylammonium (20 mM). 4. A Ca2+ transient induced by repetitive action potentials was increased asymptotically in amplitude and progressively in duration by increasing the number of spikes, and was slower in time course than the associated Ca(2+)‐dependent K+ current. 5. Scanning a single horizontal line across the cytoplasm with an ultraviolet argon ion laser (351 nm) and recording Indo‐1 fluorescence with a confocal microscope demonstrated an inward spread of a rise in [Ca2+]i following a tetanus. 6. Both single spike‐ and tetanus‐induced Ca2+ transients were abolished in a Ca(2+)‐free solution, while single or repetitive transient rises in [Ca2+]i induced by caffeine (5‐10 mM) were generated under the same conditions. 7. Ryanodine (10‐50 microM) did not affect tetanus‐induced Ca2+ transients, whereas it blocked completely the caffeine‐induced oscillation of [Ca2+]i. 8. Ca2+ transients induced by a tetanus in Ringer solution were independent of the interval from the preceding tetanus. The amplitude of Ca2+ transients induced by a tetanus in the presence of caffeine (5 mM) was equal to, or greater than, that generated in Ringer solution in any of the phases of [Ca2+]i oscillation. 9. It is suggested that under the physiological conditions here, the induction of action potentials does not cause the release of Ca2+ in the cells of the freshly excised bullfrog sympathetic ganglion, and that Ca(2+)‐buffering systems contribute not only to lowering a transient rise in [Ca2+]i but also to sustaining an increased [Ca2+]i after a large Ca2+ load into the cell.
Comparison of skeleto‐fusimotor innervation in cat peroneus brevis and peroneus tertius muscles.
Authors: Emonet‐Dénand F , Petit J , Laporte Y
Published: December 2014

1. The skeleto‐fusimotor or beta innervation was compared in cat peroneus brevis and peroneus tertius muscles, which differ in their composition of fatigue‐resistant motor units; the slow (S) units predominate in brevis and the fast units (FR) in tertius. 2. In four brevis muscles, of thirty‐four beta‐axons (from a total of 114 axons supplying extrafusal muscle fibres) twenty‐nine were dynamic (beta D) and only five static (beta S). In contrast, in three tertius muscles, of twenty‐five beta‐axons (from a total of 82 axons) twelve were static and thirteen dynamic. 3. In a population of thirty‐five brevis and thirty tertius spindles, the proportion of beta D‐innervated spindles was greater in the brevis (68.5%) than in the tertius (50%) whereas that of beta S‐innervated spindles was greater in the tertius (40%) than in the brevis (17.1%). In a population of thirty‐two brevis and twenty‐seven tertius spindles in which the presence of bag1 fibres was deduced from the existence of a dynamic innervation, the proportion of spindles innervated by beta D‐axons was 80% in the brevis and 62% in the tertius. 4. In both muscles, the number of beta D effects was greater than that of beta S effects. beta S‐axons were rarely found to supply more than one spindle whereas beta D‐axons supplying more than one spindle (up to four) were common. Spindles were often coinnervated by beta D‐ and beta S‐axons.(ABSTRACT TRUNCATED AT 250 WORDS)
Responses of macaque ganglion cells to movement of chromatic borders.
Authors: Valberg A , Lee B B , Kaiser P K , Kremers J
Published: December 2014

1. We have measured responses of macaque ganglion cells to moving borders under conditions designed to simulate the minimally distinct border (MDB) task. 2. Extending previous results, we show that minimization of responses of phasic ganglion cells of the magnocellular (MC)‐pathway obey the photometric laws of transitivity and additivity. 3. To equal luminance borders, a residual response was present in MC‐pathway cells analogous to the second harmonic response seen in these neurones with temporal chromatic modulation. It was proportional to the tritanopic purity difference (magnitude of delta Pt, the rectified middle‐ to long‐wavelength cone opponent signal) between the two colours on either side of the border. For a delta Pt of one, the mean residual response was equivalent to the response evoked by achromatic borders of about 14% luminance contrast. Both these properties of the MC‐pathway closely resemble psychophysical estimates as to the distinctness of equal luminance borders. 4. We show how MC‐pathway cell responses could be used centrally to support the MDB task. It was difficult to generate a model from responses of tonic ganglion cells of the parvocellular (PC)‐pathway which would support the task. 5. The MDB task is still possible psychophysically after blurring the retinal image. Although blurring the border spatially smeared the responses of MC‐pathway ganglion cells and reduced their amplitude, responses still went through a minimum close to equal luminance. Thus, blurring the image did not affect the ability of MC‐pathway cells to support the task. Blurring the retinal image decreased the 'sharpness' of the border response of tonic, PC‐pathway ganglion cells, but response amplitude was unaffected. Response features indicative of centre‐surround organization were attenuated. A central mechanism reliant on centre‐surround field structure of PC‐pathway cells would thus not be able to support the task after blurring. 6. Taken together, these results strongly suggest that the MC‐pathway forms the sole physiological substrate of the MDB task, and any contribution of the PC‐pathway is, indeed, minimal.
Cell volume changes upon sodium pump inhibition in Helix aspersa neurones.
Authors: Alvarez‐Leefmans F J , Gamiño S M , Reuss L
Published: December 2014

1. Identified neurones of the suboesophageal ganglia of Helix aspersa were loaded with tetramethylammonium (TMA+). Experimentally induced changes in cell water volume and membrane potential were measured continuously by monitoring changes in intracellular [TMA+] using ion‐sensitive double‐barrelled microelectrodes. The technique allowed measurements of cell water volume changes of less than 5%. 2. Exposure to hyperosmotic (up to +24%) or hyposmotic (up to about ‐10%) solutions caused reversible decreases and increases in cell water volume respectively, which agreed with near‐ideal osmometric behaviour. Upon exposure to hyposmotic solutions whose osmolality was decreased by 30‐40%, the cell water volume increased to maximum values below those expected for ideal osmometric behaviour and exhibited partial regulatory volume decrease. 3. The sodium pump was inhibited in twenty identified neurones by sustained exposure to 1 mM ouabain. In every case ouabain caused cell membrane depolarization, as expected for inhibition of an electrogenic sodium pump. 4. Upon pump inhibition most cells (n = 14) shrank by up to 13% of their initial water volume. In five of these cells, shrinkage was preceded by one or more short‐lived swelling phases. In two other neurones short‐lived swelling was followed by cell volume recovery without appreciable shrinkage. In four out of the twenty cells, there were no measurable volume changes. 5. The lack of an initial swelling phase in the cells that shrank, as well as the absence of detectable volume changes in some of the neurones, was not due to loss of ion‐selective electrode sensitivity since predictable changes in cell volume elicited by osmotic challenges were monitored in the same cells. 6. It is concluded that neurones can be endowed with ouabain‐insensitive mechanisms of volume control, whose activation following Na+ pump inhibition prevents them from short‐term swelling and lysis.
Role of M1 muscarinic receptors in the parasympathetic control of colonic motility in cats and rabbits.
Authors: Blanquet F , Gonella J
Published: December 2014

1. The effects of pirenzepine (a selective blocking agent of M1 muscarinic receptors) were studied on excitatory junction potentials (EJPs) and inhibitory junction potentials (IJPs) elicited on colonic smooth muscle by stimulation of efferent parasympathetic nerve fibres in anaesthetized cats and rabbits. 2. Pirenzepine (25 micrograms kg‐1 to 0.2 mg kg‐1, i.v.) decreased the amplitude of EJPs or abolished them. In pirenzepine, parasympathetic stimulation elicited IJPs in most cases. 3. In both species, pirenzepine initiated spontaneous IJPs, indicating an increase in the activity of the non‐adrenergic, non‐cholinergic (NANC) inhibitory neurones. 4. The results suggest that M1 muscarinic receptors are involved in synaptic transmission within intramural plexuses, at interneuronal synapses in the parasympathetic excitatory pathway to colonic smooth muscle, but are not involved in the pathway to the NANC inhibitory neurones. The facilitation of IJPs by pirenzepine suggests that, under normal physiological conditions, NANC neurones are tonically inhibited by an intramural nervous circuit involving M1 muscarinic receptors.
Effects of internal and external Na+ ions on inwardly rectifying K+ channels in guinea‐pig ventricular cells.
Authors: Matsuda H
Published: December 2014

1. The effects of internal and external Na+ ions on the inwardly rectifying K+ channel were studied in guinea‐pig ventricular cells. 2. Single‐channel currents through the inwardly rectifying K+ channel were recorded in the open cell‐attached or inside‐out configuration at 150 mM internal K+ and either 150 or 25 mM external K+. Internal Na+, at a concentration of 5‐40 mM, reduced the unitary amplitude of the outward current. No increase in open‐channel current noise was detected with the filter cut‐off frequency of 3 kHz. Substate behaviour seen with internal Mg2+ at a micromolar level was not observed. The inward currents were little affected by internal Na+. 3. The unitary current‐voltage relation rectified inwardly in the presence of internal Na+ in a concentration‐dependent manner. 4. Outward unitary currents were normalized to those measured in the absence of Na+. The normalized current‐voltage relation was shifted in the negative direction by 20‐25 mV by decreasing external K+ from 150 to 25 mM, indicating that the blocking effect increases with low external K+ when compared at a fixed voltage. 5. The normalized current‐Na+ concentration curve was fitted by a one‐to‐one binding curve at each voltage. In a semi‐logarithmic plot of dissociation constant versus membrane potential, data points for 150 and 25 mM external K+ were fitted by straight lines with nearly the same slope. The dissociation constant at 0 mV is 154 mM in 150 mM external K+ and 89 mM in 25 mM external K+. The voltage dependence of dissociation constants gives a value for the effective valency of the Na+ ion of around 0.5. 6. To study effects of external Na+, single‐channel currents were recorded with pipette solutions containing 125 mM Na+, 125 mM choline or 125 mM N‐methyl‐D‐glucamine (NMDG) in addition to 25 mM K+. Current amplitude was smaller with choline than with Na+ or NMDG. The reduction in current amplitude with choline was more evident in the inward current, resulting in a stronger outward rectification of the current‐voltage relation. This finding and prolonged mean open time (see Summary point 7) was interpreted by assuming that choline is an open‐channel blocker. 7. The lifetimes of the openings in the inward currents were distributed according to a single exponential. The mean open time with Na+ was similar to that with NMDG, which decreased with hyperpolarization. The mean open time with choline was much longer and less voltage dependent.(ABSTRACT TRUNCATED AT 400 WORDS)
Spatial integration and sensitivity changes in the human rod visual system.
Authors: Sharpe L T , Whittle P , Nordby K
Published: December 2014

1. The factor by which increment threshold rises with increasing background intensity is less if the target is small than if it is large. The difference is usually attributed to a reduction in the area over which visual signals are integrated as the visual system light adapts. Recently, however, it has been argued that the difference in slope may instead be caused by an increase in the gain of the local response function with light adaptation. 2. To test this hypothesis in the rod‐driven visual system, we compared monoptic, small and large target increment thresholds, and dichoptic, large target brightness matches, measured as a function of background intensity in a typical, complete achromat, who has no cone vision. 3. The dichoptic brightness matches were made using a large target of a similar intensity to the threshold intensity of the small target. If local intensity is important, the large target brightness matching curve should be more similar to the shallow, small target threshold curve. But, if changes in spatial integration are important, the brightness matching curve should be similar to the steeper, large target threshold curve. 4. The slope of the large (1.85 deg) target increment threshold functions measured with either 200 or 50 ms test flashes were steeper than those of the small (10 min of arc) target functions by 0.10 (on logarithmic co‐ordinates) or about 15%. 5. The logarithmic slopes of the dichoptic brightness curves were also slightly steeper than the small target increment functions. This is contrary to the local response (only) hypothesis, which predicts that the brightness curve should have the same slope as the small target function because the luminance of the targets in the two cases is the same. 6. We conclude that there must be a change in spatial integration in the rod visual system during light adaptation, over and above that due to local gain changes.
Long‐term changes in synaptic strength along specific intrinsic pathways in the cat visual cortex.
Authors: Hirsch J A , Gilbert C D
Published: December 2014

1. The dense system of horizontal connections that arise and course within the striate cortex are thought to inform single cells about stimuli arising in disparate points in visual space and to modulate responses evoked from within the receptive field. To learn whether or not the strength of the horizontal connections could vary over the long term, and if such changes could affect the integration of vertical, interlaminar inputs, we have recorded intracellularly from the superficial layers in slices of the adult cat's visual cortex. 2. The monosynaptic EPSP evoked by stimulating horizontal fibres showed long‐term facilitation in twelve of the twenty cells that were conditioned by repetitively pairing synaptic responses with depolarizing pulses of current; the maximum increase observed was 200%. Strong inhibition present in the postsynaptic response usually indicated that facilitation would not occur. 3. In instances where horizontal input evoked both mono‐ and polysynaptic EPSPs, both early and late events showed facilitation, with the most dramatic enhancement contributed by the polysynaptic components. 4. For the twenty‐eight cells whose responses to stimulation of interlaminar as well as horizontal pathways were assessed, all were found to receive non‐overlapping inputs from each source. Conditioning produced long‐term changes in the strength of the interlaminar inputs. 5. Changes in synaptic strength were usually confined to the conditioned pathway, though in four out of twenty‐six times we observed heterosynaptic facilitation of polysynaptic EPSPs. 6. The conditioning protocol led to lasting depression rather than facilitation in three out of eleven instances; the reduction was only observed in the multisynaptic components. 7. We suggest that the synaptic changes observed here may be related to certain dynamic changes in receptive field properties that have been characterized in vivo.
Autoregulation and non‐homeostatic behaviour of renal blood flow in conscious dogs.
Authors: Persson P B , Ehmke H , Kirchheim H R , Janssen B , Baumann J E , Just A , Nafz B
Published: December 2014

1. Spontaneously occurring haemodynamic variations within 4 h affecting renal blood flow (RBF) were compared with externally induced short changes of renal artery pressure (RAP) in conscious resting dogs. 2. In all animals in which RAP was servo‐controlled (n = 6), perfect autoregulation of RBF was observed. 3. In all 4 h recordings of spontaneous renal blood flow (n = 9), certain combinations of blood pressure and blood flow occurred remarkably frequently as indicated by three‐dimensional frequency distributions. 4. Cluster analysis demonstrated significant differences between these areas of accumulation (P < 0.001). The average number of 'set points' per 4 h session was 3.1 +/‐ 0.3. 5. The shift from one set point to another is probably mediated by multiple control systems impinging on renal haemodynamics as suggested by 1/f fluctuations. 6. In seven dogs, an additional renal venous catheter allowed measurements of the arterial‐venous (A‐V) oxygen partial pressure (PO2) difference as an indicator of the renal metabolic demand. An inverse relationship between A‐V PO2 difference and RBF (Y = X(‐0.034) + 40.9, r = ‐0.9, P < 0.001) was found, indicating that the metabolic demands vary little (if at all) between the different set points. 7. The presented data suggest a modified view of renal homeostasis. There exist distinct combinations between RBF and RAP, which are very stable. Autoregulation merely buffers the fluctuations around these set points.
Repriming of L‐type calcium currents revealed during early whole‐cell patch‐clamp recordings in rat ventricular cells.
Authors: Tiaho F , Nargeot J , Richard S
Published: December 2014

1. The establishment of the whole‐cell patch‐clamp recording configuration (WCR) revealed a type of inhibition to which L‐type Ca2+ channels were subject in static rat ventricular myocytes before obtaining the WCR. 2. Immediately after membrane disruption (< 10 s), the Ca2+ current (ICa) was absent but gradually increased in amplitude to reach its final waveform (amplitude and kinetics) 2‐3 min after the WCR was reached. 3. Three distinct phases (P) were identified. First, no inward but an outward current, blocked (1‐2 min) by Cs+ dialysing from the patch pipette (P1), was recorded. Second, overlapping with (P1), ICa increased dramatically to reach a maximum peak amplitude within 2‐3 min (P2). Concomitantly, its rate of decay, initially monoexponential and slow, became biexponential owing to the appearance of a fast component of inactivation (P3). Complete interconversion between slow and fast components sometimes occurred. 4. Changes in current waveform were not related to voltage loss or series resistance variation, and suppression of an outward current (P1) was unlikely to account for P2 and P3. 5. The run‐up of ICa was independent of the nature of the permeating ions, the membrane holding potential, depolarization, rate of stimulation, the intracellular Ca2+, ATP, Mg2+, Cs+ and the pH of the pipette solution. Since large Ca2+ currents were recorded using the perforated patch technique, the run‐up of ICa is not explained by the wash‐out of an inhibitory endogenous macromolecule during cell‐pipette exchanges. 6. Pharmacological manipulations, including the use of Ca(2+)‐Ba(2+)‐EGTA and exposure of the cells to isoprenaline and/or Bay K 8644 prior to recording, did not alter the mechanism primarily responsible for build‐up. Unrepriming of channel activity was required before these modulations could be effective. 7. Currents could however be instantly augmented when cells were extracellularly superfused during the run‐up step. The wash‐out of an inhibitory agent originating in the cell itself (such as H+, NH4+ and lactate) and accumulating in the extracellular microenvironment of the cells seems unlikely. Rather, we suggest that pressure‐induced mechanostimulation may be involved in the restoration of Ca2+ channel activity.
Myelinated primary afferents of the sacral spinal cord responding to slow filling and distension of the cat urinary bladder.
Authors: Häbler H J , Jänig W , Koltzenburg M
Published: December 2014

1. A total of sixty‐five sacral afferent neurones with myelinated fibres supplying the urinary bladder was recorded from the sacral roots S2 in anaesthetized cats. All afferent units were identified with electrical stimulation of the pelvic nerve. The discharge properties were quantitatively evaluated using slow filling at rates of 1‐2 ml min‐1 and isotonic distension to preset pressure levels. Eight afferents were studied prior to and after acute sacral de‐efferentation of the urinary bladder. 2. All afferent units were silent when the bladder was empty and responded in a graded manner to an increase of intravesical pressure. During slow filling the level of afferent activity correlated closely with the level of the intravesical pressure. All afferents behaved like slowly adapting mechanoreceptors with both a dynamic and static component of their discharge. With the exception of two units the intraluminal pressure threshold was below 25 mmHg. Thus virtually all myelinated afferents respond in the pressure range that is reached during a non‐painful micturition cycle. 3. The stimulus‐response functions of the afferents were similar regardless of whether intravesical pressure was increased by slow filling or by distension. However, during slow filling stimulation response functions often exhibited steeper slopes between 5 and 25 mmHg indicating that relatively small changes of intravesical pressure result in large changes of afferent activity. Nevertheless, all units displayed monotonically increasing stimulus response functions throughout the innocuous and noxious pressure level. 4. The stimulus‐response functions of the afferent neurones did not change after acute de‐efferentation of the urinary bladder, although the rapid phasic fluctuations of afferent activity that are produced by small contractions of the urinary bladder under normal conditions largely disappeared. This means that contractions and distension activate the afferent endings by a common mechanism. 5. It is concluded that the myelinated sacral afferents of the urinary bladder form a homogeneous population which encodes all information necessary for the normal regulation of this organ. Furthermore, this set of afferents mediates all sensations which may reach consciousness within a normal micturition cycle.
Effects of osmolality and ionic strength on the mechanism of Ca2+ release in skinned skeletal muscle fibres of the toad.
Authors: Lamb G D , Stephenson D G , Stienen G J
Published: December 2014

1. The effects of increased osmolality and ionic strength on the mechanism of Ca2+ release were examined in mechanically skinned skeletal muscle fibres of the toad at 23 degrees C. Ca2+ release was induced by depolarizing the transverse tubular (T‐) system by ionic substitution. 2. Increasing the osmolality of the ‘myoplasmic’ solution about four times (to 955 mosmol/kg), by addition of 700 mM sucrose to the standard potassium (K‐)HDTA solution (HDTA: hexamethylenediamine‐tetraacetate), only depressed the depolarization‐induced response by about 46%. Much of this decrease could be attributed to a reduction in the Ca(2+)‐sensitivity of the contractile proteins at this high osmolality. 3. Addition of > 400 mM sucrose itself often induced substantial Ca2+ release and a transient tension response. This 'spontaneous’ release was (a) greatly enhanced when the sarcoplasmic reticulum (SR) had been heavily loaded with Ca2+, (b) little affected by inactivation of the voltage sensors by prolonged or permanent depolarization of the T‐system and (c) blocked by Ruthenium Red (10 microM). 4. When both the osmolality and ionic strength were increased, by increasing the K‐HDTA concentration, the depolarization‐induced force was greatly reduced (to 35% at 818 mosmol/kg and 5% at 1095 mosmol/kg). Most of this reduction could be directly attributed to the substantially reduced maximum force and Ca2+ sensitivity of the contractile apparatus. 5. The small amount of releasable Ca2+ remaining in the SR after a single depolarization in a high‐HDTA solution with 1 mM EGTA (to chelate the released Ca2+), indicated that depolarization could still elicit massive Ca2+ release at high ionic strength and osmolality (at 1 mM free Mg2+). 6. In contrast, when the total Mg2+ and ATP concentrations were raised about threefold (free [Mg2+] increased 2.7‐fold) along with the osmolality and ionic strength, the ability of depolarization to elicit Ca2+ release was greatly hindered. 7. Osmotic compression of the skinned fibres to their in situ diameter by addition of 4% polyvinylpyrrolidone (PVP‐40), substantially potentiated the depolarization‐induced force responses, due partly to an increase in the Ca(2+)‐sensitivity of the contractile apparatus. 8. These results indicate how increased intracellular osmolality, ionic strength and [Mg2+] produce the transient contraction and subsequent inhibition of tetanic tension in intact muscle fibres exposed to hypertonic solutions.
Changes of intracellular [Ca2+] during refilling of sarcoplasmic reticulum in rat ventricular and vascular smooth muscle.
Authors: Baró I , O'Neill S C , Eisner D A
Published: December 2014

1. Intracellular calcium concentration ([Ca2+]i) was measured in single myocytes isolated from either the cardiac ventricle or the mesenteric artery of the rat. 2. In both cardiac and smooth muscle, the application of caffeine produced an increase of [Ca2+]i which spontaneously decayed back to resting levels. In vascular smooth muscle cells, removal of caffeine produced a transient fall of [Ca2+]i to below the resting level. [Ca2+]i then returned to control levels. A transient undershoot of [Ca2+]i on removal of caffeine was also sometimes seen in cardiac cells. When the undershoot was absent in cardiac cells it could be induced by elevating [Ca2+]o. 3. In vascular smooth muscle cells noradrenaline increased [Ca2+]i and an undershoot of [Ca2+]i could be produced by its removal. In cardiac cells a small undershoot could sometimes be seen following the systolic Ca2+ transient produced by electrical stimulation. 4. In both cardiac and vascular cells the time constant of decay of the caffeine response (tau caff) was less than that of the recovery from the undershoot (tau us). On average the ratio tau us:tau caff was about 5 in smooth muscle. In cardiac cells the recovery of the undershoot was also considerably slower than that of the caffeine response. 5. If caffeine was removed before the rise of [Ca2+]i had fully decayed spontaneously then the magnitude of the undershoot was reduced. 6. It is suggested that the undershoot of [Ca2+]i on removal of caffeine results from refilling of the SR decreasing [Ca2+]i. The data from vascular cells can be fitted by this model if the dissociation constant, Kd, of the surface membrane Ca2+ pump for [Ca2+]i is about 1 microM. 7. Using the model, it is concluded from the ratio of the time constants shown above that the caffeine releasable content of the sarcoplasmic reticulum constitutes about 80% of total cellular calcium in both cardiac and smooth muscle.