bluuebunny/crossref_metadata_2025 huggingface dataset:
Voltage‐dependent conductances of solitary ganglion cells dissociated from the rat retina.
Authors: Lipton S A , Tauck D L
Published: December 2014

1. Ganglion cells were dissociated from the enzyme‐treated rat retina, identified with specific fluorescent labels, and maintained in vitro. Electrophysiological properties of solitary retinal ganglion cells were investigated with both conventional intracellular and patch‐clamp recordings. Although comparable results were obtained for most measurements some important differences were noted. 2. The input resistance of solitary retinal ganglion cells was considerably higher when measured with ‘giga‐seal’ suction pipettes than with conventional intracellular electrodes. Under current‐clamp conditions with both intracellular and patch pipettes, these central mammalian neurones maintained resting potentials of about ‐60 mV and displayed action potentials followed by an after‐hyperpolarization in response to small depolarizations. The membrane currents during this activity, analysed under voltage clamp with patch pipettes, consisted of five components: Na+ current (INa), Ca2+ current (ICa), and currents with properties similar to the delayed outward, the transient (A‐type), and the Ca2+‐activated K+ currents (IK, IA and IK(Ca), respectively). 3. Ionic substitution, pharmacological agents, and voltage‐clamp experiments revealed that the regenerative currents were carried by both Na+ and Ca2+. 100 nM‐1 microM‐tetradotoxin (TTX) reversibly blocked the fast spikes carried by the presumptive INa, which under voltage‐clamp analysis had classical Hodgkin‐Huxley‐type activation and inactivation. 4. Single‐channel recordings of the Na+ current (iNa) permitted comparison of these 'microscopic' events with the 'macroscopic' whole‐cell current (INa). The inactivation time constant (tau h) fitted to the averaged single‐channel recordings of iNa in outside‐out patches was slower than the tau h obtained during whole‐cell recordings of INa. 5. In the presence of 1‐40 microM‐TTX and 20 mM‐TEA, slow action potentials appeared in intracellular recordings and were probably mediated by Ca2+. The potentials were abrogated by 3 mM‐Co2+ or 200 microM‐Cd2+; conversely, increasing the extracellular Ca2+ concentration from 2.5 to 10‐25 mM or substitution of 1 mM‐Ba2+ for 2.5 mM‐Ca2+ enhanced their amplitude. ICa was measured directly in whole‐cell recordings with patch pipettes after blocking INa with extracellular 1 microM‐TTX and K+ currents with intracellular 120‐mM Cs+ and 20 mM‐TEA. 6. During whole‐cell recordings with patch electrodes, extracellular 20 mM‐TEA suppressed IK and, to a lesser extent, IA. Extracellular 5 mM‐4‐AP or a pre‐pulse of the membrane potential to ‐40 mV prior to stronger depolarization completely blocked IA.(ABSTRACT TRUNCATED AT 400 WORDS)
Field potentials generated by group II muscle afferents in the middle lumbar segments of the cat spinal cord.
Authors: Edgley S A , Jankowska E
Published: December 2014

1. A powerful projection from group II muscle afferents of hind‐limb muscles to the 3rd, 4th and 5th segments of the lumbar spinal cord has been demonstrated by focal synaptic field potential recording. 2. Field potentials were found at two locations: one in the dorsal horn (Rexed's laminae IV and V) and the other in the intermediate zone and ventral horn (Rexed's laminae VII and VIII). In the dorsal horn the field potentials were exceptionally large and were evoked only by group II afferents. At more ventral locations, they were smaller and were sometimes preceded by small field potentials evoked by group I afferents. 3. At both locations field potentials could be evoked by stimulation of a number of hind‐limb muscle nerves at strengths sufficient to activate group II afferents. However, some nerves consistently evoked more powerful effects than others and the largest potentials were from the nerves to quadriceps, sartorius and to the pretibial flexor muscles (tibialis anterior and extensor digitorum longus). Activation of articular afferents (from the knee joint nerve) or Pacinian corpuscle afferents (from the interosseous nerve) evoked small field potentials at some locations. 4. In the dorsal horn the latency of the field potentials was so short that they must have been generated monosynaptically. Field potentials in the ventral horn had longer latencies, by 0.5‐1.0 ms, but they also appear to have been monosynaptically evoked by slowly conducting intraspinal collaterals. This conclusion is based primarily on the effects of intraspinal stimulation which was found to antidromically activate afferents with the appropriate latencies and thresholds. 5. Evidence is presented that the dorsal and ventral field potentials are generated by afferents whose receptors can be activated by small (less than 100 micron) muscle stretches.
Effects of 2‐ketoisocaproate on insulin release and single potassium channel activity in dispersed rat pancreatic beta‐cells.
Authors: Ashcroft F M , Ashcroft S J , Harrison D E
Published: December 2014

1. The effects of the insulin secretagogue 2‐ketoisocaproate, and of arginine, on insulin release, intracellular adenosine triphosphate (ATP) concentration and the activity of single K channels in cell‐attached membrane patches have been studied in primary cultures of beta‐cells from adult rat islets of Langerhans. 2. Insulin secretion was significantly increased by 2‐ketoisocaproate (20 mM). The time course of this release was biphasic. Arginine (20 mM) did not stimulate insulin secretion. 3. In the absence of 2‐ketoisocaproate (or arginine), two kinds of K channel were regularly observed in cell‐attached membrane patches held at the cell resting potential: a channel of approximately 20 pS conductance and a channel of 50 pS conductance ([K]o = 140 mM, room temperature). 4. Addition of 2‐ketoisocaproate (20 mM) to the bath suppressed the activity of the 50 pS channel and initiated action potentials. Arginine (20 mM) was without effect. 5. The intracellular concentration of ATP was increased significantly by 2‐ketoisocaproate (20 mM) but not by arginine (20 mM). 6. It is suggested that, like glucose, 2‐ketoisocaproate depolarizes the beta‐cell and mediates insulin secretion by reducing the open probability of the 50 pS K channel. The results are also consistent with the idea that both secretagogues inhibit this channel by increasing the cytoplasmic concentration of ATP.
The sarcomere length‐tension relation determined in short segments of intact muscle fibres of the frog.
Authors: Edman K A , Reggiani C
Published: December 2014

1. Single fibres isolated from the tibialis anterior muscle of Rana temporaria were stimulated to produce a 1 s fused tetanus, while a short (ca. 0.5 mm) segment of the fibre was held at constant length. The segments were defined by opaque markers of hair that were placed on the fibre surface. The distance between two adjacent markers (one segment) was monitored by means of a photo‐electric recording system. The length of a given segment could be controlled to within 0.2% of the segment's length by adjusting the over‐all length of the fibre by means of an electromagnetic puller and servo system. 2. Segments producing constant force (no 'tension creep') during length‐clamp recording were studied at different striation spacings within the following ranges of sarcomere length: 2.20‐3.70, 1.90‐2.45 and 1.50‐2.20 microns. The absence of tension creep suggested (Edman & Reggiani, 1984 a) that the sarcomere pattern remained stable within the length‐clamped segment during contraction at different lengths. 3. The tetanic force of a given length‐clamped segment was consistently found to increase, as the sarcomere length was reduced from 2.20 to 1.98‐2.02 microns, the mean increase in force being 6.9 +/‐ 0.4% (S.E. of mean, thirty‐two segments). By further decreasing the sarcomere length active force was reduced. 4. The increase in force‐producing capability between 2.20 and 2.00 microns sarcomere length was further explored by recording the maximum rate of force redevelopment, dF/dtmax, after a quick release during the plateau of a fixed‐end tetanus. dF/dtmax varied with sarcomere length between 2.20 and 2.00 microns in the same way as the isometric force of a short, length‐clamped segment, increasing by ca. 10% over this range. This finding provides further support for the view that the fibre's capacity to produce force is not constant between 2.20 and 2.00 microns sarcomere length. 5. The descending limb of the length‐tension relation extended between 2.00 and approximately 3.65 microns sarcomere length. Its middle, straight portion (between 2.30 and 3.30 microns sarcomere spacings) extrapolated to zero tension at 3.49 microns sarcomere length. The upper and lower portions of the descending limb were slightly curved (at sarcomere lengths less than 2.30 and greater than 3.30 microns, respectively) giving the descending limb a symmetrical sigmoid appearance.(ABSTRACT TRUNCATED AT 400 WORDS)
Actions of neuropeptide Y on innervated and denervated rat tail arteries.
Authors: Neild T O
Published: December 2014

1. Neuropeptide Y caused a dose‐dependent contraction and depolarization of the smooth muscle of the rat tail artery. 2. 30 nM‐neuropeptide Y increased the contraction caused by either nerve‐released noradrenaline or smooth muscle action potentials. 3. 30 nM‐neuropeptide Y did not change the amplitude or rate of rise of the smooth muscle action potential. It did not change the amplitude of small excitatory junction potentials, suggesting that it did not affect neurotransmitter release. 4. 30 nM‐neuropeptide Y increased the contraction caused by exogenous noradrenaline, 5‐hydroxytryptamine and K in concentrations that gave submaximal contractions. It did not affect the response to higher concentrations that gave maximal or near‐maximal contractions.
Temporal patterning in the responses of gracile and cuneate neurones in the cat to cutaneous vibration.
Authors: Ferrington D G , Horniblow S , Rowe M J
Published: December 2014

1. Recordings were made in decerebrate cats from gracile and cuneate neurones responding to vibration‐induced inputs from Pacinian corpuscle (P.c.) receptors of the hind‐limb and forelimb footpads. The two groups of neurones were compared, in particular for their capacities for responding to cutaneous vibration with phase‐locked impulse patterns. 2. In both nuclei the P.c. neurones were most sensitive to vibration in the range 80 to greater than 600 Hz. Stimulus‐response relations were similar for the two groups, as were measures derived from these relations such as response levels, absolute thresholds and the dynamic range (defined as the vibration amplitude range over which responses were graded). 3. At frequencies up to 300‐400 Hz, responses for some neurones in both nuclei remained well phase locked to the vibration; however, quantitative analysis using a factorial analysis of variance indicated that the phase locking was poorer in gracile than cuneate neurones. 4. In both nuclei there was marked variability from neurone to neurone in measures of phase locking which may reflect variations in the extent of convergence of P.c. fibres upon different target neurones. For neurones in either nucleus that had comparatively tight phase locking of responses to vibration it is proposed that their output is functionally dominated by one or a few of their convergent P.c. input fibres.
Integrative processing of vibratory information in cat dorsal column nuclei neurones driven by identified sensory fibres.
Authors: Ferrington D G , Rowe M J , Tarvin R P
Published: December 2014

1. In decerebrate or anaesthetized cats, the vibration‐induced responses of dorsal column nuclei neurones were examined, first, when their input came from simultaneously recorded pairs or other combinations of identified Pacinian corpuscle (P.c.) afferent fibres of the interosseous nerve, and secondly, when different convergent sets of P.c. fibres were engaged by footpad vibration. 2. Suprathreshold actions were observed on individual dorsal column nuclei neurones from two or more identified P.c. fibres. Recruitment of these convergent fibres usually led to summation in the dorsal column nuclei neurone as reflected in higher response levels compared with those evoked by single‐fibre inputs. 3. When the input was increased from one to two or more identified P.c. fibres the dorsal column nuclei neurones could retain a single, dominant phase of response to high‐frequency (greater than 100 Hz) vibration even though these fibres, in isolation, evoked responses in the target neurone at substantially different latencies. However, on average, phase locking was significantly tighter in response to single‐fibre input than to multiple P.c.‐fibre input. 4. Dorsal column nuclei neurones were also able to retain phase‐locked responses to high‐frequency vibration when phase differences between different convergent inputs were systematically introduced to alter the degree of synchrony in the activity arriving over convergent, identified P.c. fibres. 5. When the input to dorsal column nuclei neurones came from the skin it was found that with the recruitment of two converging sets of P.c. fibres the dorsal column nuclei neurones were able to retain phase‐locked responses to high‐frequency vibration even when phase shifts were introduced between the two sets of P.c. inputs. 6. In conclusion, the observed integrative processing by dorsal column nuclei neurones of vibration‐induced inputs arriving over identified, convergent P.c. fibres, or sets of P.c. fibres, is consistent with our hypothesis that the retention of phase‐locked responses to vibration at frequencies greater than or equal to 100 Hz may reflect the functional domination of the target neurone by just one or a few of its convergent input fibres.
Persistent calcium‐sensitive potassium current and the resting properties of guinea‐pig myenteric neurones.
Authors: North R A , Tokimasa T
Published: December 2014

1. Intracellular recordings were made from neurones in the guinea‐pig myenteric plexus which show a long‐lasting after‐hyperpolarization following the action potential (AH neurones). In most experiments membrane currents were measured using a single‐electrode voltage clamp. Tetrodotoxin was present. 2. A step depolarization (10‐15 mV, 5‐10 s) from a holding potential close to the resting level (typically ‐60 mV) caused a slowly developing outward current. The current increased exponentially with a time constant of about 1.3 s at ‐50 mV. At the termination of the step the current declined over a similar time period (time constant congruent to 2.5 s). Hyperpolarizing step commands resulted in a slowly declining outward current (tau congruent to 3.5 s at ‐70 mV) which developed again at the termination of the hyperpolarization (tau congruent to 2.1 s at ‐60 mV); these tail currents reversed at the potassium equilibrium potential. 3. The current was not observed in solutions containing no calcium, high magnesium concentrations and cobalt. It did not inactivate during changes in holding potential of up to 5 min. The current is therefore called the persistent calcium‐sensitive potassium current. 4. A brief depolarizing command to less‐negative potentials (typically to ‐10 mV for 10‐30 ms) was followed by a potassium current which increased and decreased according to the sum of two exponentials having time constants tau on congruent to 0.4 s and tau off congruent to 2.5 s. This after‐current disappeared in calcium‐free, high‐magnesium and cobalt solution. 5. Both the after‐current and the persistent calcium‐sensitive current were similarly sensitive to tetraethylammonium ions, being unaffected by 5 mM but substantially reduced by 20 mM solutions. The time constant of decline of the persistent calcium‐sensitive current at the end of a depolarizing step was not different from tau off for the after‐current; these time constants had a similar sensitivity to voltage and temperature. 6. The conductance underlying the after‐current became progressively smaller as the persistent calcium‐sensitive current was increased by membrane depolarization. In a given neurone, the sum of the two conductances was constant. This finding implies that the persistent calcium‐sensitive potassium conductance is the same conductance as that which is increased during the after‐hyperpolarization.
Beta‐adrenergic blockade restores glucose's antiketogenic activity after exercise in carbohydrate‐depleted athletes.
Authors: Adams J H , Irving G , Koeslag J H , Lochner J D , Sandell R C , Wilkinson C
Published: December 2014

1. The development of post‐exercise ketosis is not abolished by the ingestion of glucose immediately after exercise, despite inducing high insulin/glucagon ratios in the peripheral (and therefore by implication in the portal) blood. 2. To investigate the possibility of autonomic control of the liver influencing its sensitivity to the major counter‐regulatory hormones, we administered 50 g glucose, either on its own, or together with 0.5 mg prazosine, 40 mg propranolol, or 15 mg propantheline, to forty‐seven 48 h carbohydrate‐starved athletes who had just run 25 km. 3. The blood 3‐hydroxybutyrate concentration rose from 0.30 +/‐ 0.05 (mean +/‐ S.E. of mean) to 0.52 +/‐ 0.08 mmol/l with exercise, and then to 1.32 +/‐ 0.40 mmol/l at 6 h after exercise in subjects who had ingested only glucose after exercise. 4. The effects of prazosine and propantheline on the blood ketone body concentration at 2 h after exercise was not statistically significant. Propranolol, on the other hand, significantly lowered the blood 3‐hydroxybutyrate concentration (compared with controls) to 0.09 +/‐ 0.03 mmol/l at 3 h (P less than 0.01), and 0.35 +/‐ 0.08 mmol/l at 6 h (P less than 0.01) after exercise. 5. The plasma insulin, glucagon, glucose and free fatty acid concentrations were unaffected by propranolol, indicating that the antiketogenesis was the result of a direct effect on ketone body metabolism. 6. Since beta‐adrenergic blockade has not previously been shown to have antiketogenic activity, except in somatostatin‐induced hyperketonaemia, it is concluded that its effectiveness in post‐exercise ketosis can probably be ascribed to a functional hepatic insulin and glucagon deficiency.
Role of large arteries in regulation of blood flow to brain stem in cats.
Authors: Faraci F M , Heistad D D , Mayhan W G
Published: December 2014

1. The goal of this study was to examine the regulation of resistance in the large arteries and small vessels that supply the brain stem. 2. We used a new method in anaesthetized cats to measure blood flow to the medulla (microspheres) and pressure (servo‐null) in branches of the basilar artery that supply the medulla. Resistance was determined during normocapnia, hypercapnia, hypocapnia and seizures (produced with intravenous bicuculline). 3. Pressure in arteries that supply the medulla (150 microns internal diameter) was 71 +/‐ 4% (mean +/‐ S.E. of mean) of aortic pressure and large artery resistance was 31 +/‐ 4% of the total resistance in the medulla. Hypercapnia and seizures decreased large artery resistance by 67 and 50%, respectively, and hypocapnia increased large artery resistance by 58%. Small vessel resistance decreased by 82% during hypercapnia and by 43% during seizures, and increased by 96% during hypocapnia. 4. Thus, resistance of the large arteries (greater than 150 microns diameter) accounts for about one‐third of the total vascular resistance in the brain stem. Both large arteries and small vessels respond to alterations in arterial carbon dioxide tension and seizures, and contribute to the regulation of blood flow to the brain stem.
Conductance and kinetics of delayed rectifier potassium channels in nodal cells of the rabbit heart.
Authors: Shibasaki T
Published: December 2014

1. The delayed rectifier K+ current (IK) of single pace‐maker cells from the sino‐atrial node and the atrioventricular node of the rabbit heart was investigated using the whole‐cell and cell‐attached configurations of the patch‐clamp technique. 2. The activation kinetics of the macroscopic IK were not altered by varying the extracellular K+ concentration ([K+]o) between 5.4 and 150 mM. The amplitude of the tail current of IK, however, was about 10‐fold larger at a [K+]o of 150 mM than that at a [K+]o of 5.4 mM. 3. By using a high‐[K+]o solution, inward single‐channel currents were observed on repolarization from potentials positive to ‐40 mV. The current‐voltage (I‐V) relation was linear over the negative potential range and the reversal potential estimated by extrapolating the I‐V curve was shifted by about 60 mV for a 10‐fold increase in [K+]o, indicating that the channel was highly selective for K+. 4. The single‐channel conductance was 11.1 pS at a [K+]o of 150 mM and varied in proportion to the square root of [K+]o. The total number of channels was estimated as approximately 1000 per cell (0.7/micron 2). On repolarization, the averaged single‐channel current disappeared with a time constant similar to that of the macroscopic tail current of IK. 5. At potentials between ‐50 and ‐100 mV, the open and closed times of the single channel fitted well with single‐exponential and biexponential distributions, respectively. As the membrane was progressively depolarized, the open time was shortened while the closed time was prolonged, suggesting a decrease of open probability. These changes were in the opposite direction to those expected from the delayed rectifier K+ current which progressively increases in magnitude at more positive potentials. 6. At the beginning of the macroscopic tail current, a transient increase of the inward current was found to precede the time‐dependent decrease. This rapid initial change can be attributed to a quick removal of inactivation of IK which had occurred during the depolarizing pulse. This inactivation gate of the channel has very fast kinetics and could be responsible for the inward‐going rectification observed in the 'fully activated' IK.
Voltage‐dependent magnesium block of adenosine‐triphosphate‐sensitive potassium channel in guinea‐pig ventricular cells.
Authors: Horie M , Irisawa H , Noma A
Published: December 2014

1. The adenosine‐5'‐triphosphate (ATP)‐sensitive K+ channel of guinea‐pig ventricular cells was examined in the presence and absence of internal Mg2+ or Na+ using an open cell‐attached configuration of the patch‐clamp technique. 2. Millimolar concentrations of internal Mg2+ ([Mg2+]i) produced marked fluctuations in the outward current, and the amplitude of the open‐channel current was reduced with increasing [Mg2+]i. Millimolar Na+ applied internally also decreased the mean amplitude of the outward current, but the increase in current noise was not obvious. These effects became larger when the membrane potential was shifted to be more positive from the K+ equilibrium potential (EK). At potentials negative to EK the inward current was affected by neither internal Mg2+ nor Na+. 3. The external application of Na+, Mg2+ or Ca2+, however, failed to affect the single‐channel current. 4. After removal of both internal Mg2+ and Na+, the mean open‐channel current‐voltage relationship became virtually linear. Referring to these unblocked values, relative amplitudes were determined at different levels of [Mg2+]i or [Na+]i. The dose‐response relations gave a Hill coefficient of approximately 1 for Mg2+ block and approximately 2 for Na+ block. The half‐maximum concentrations (Kh) for both Mg2+ and Na+ block were shifted to lower values with increasing positive potentials. 5. The power‐density spectrum of the open‐channel current noise induced by internal Mg2+ showed a Lorentzian function with a corner frequency above 1 kHz, suggesting that the current noise is due to rapid fluctuations of open‐channel current between blocked and unblocked states. The corner frequencies gave Mg2+ block and unblock rate constants which were of the order of 10(7) M‐1 s‐1 and 10(4) s‐1, respectively. 6. With increasing external K+ concentration ([K+]o) from 0 to 140 mM the current fluctuations became less prominent, and Kh for Mg2+ block was shifted to higher values. Raising [K+]o enhanced the unblock rate derived from the noise analysis while the block rate was not significantly altered. 7. The above findings could be explained by assuming a binding site for one Mg2+ or two Na+ located 30‐35% of the electrical drop across the membrane from the inner mouth of the channel, thereby resulting in the ionic block of K+ passage. An apparent inward rectification observed in the single‐channel current‐voltage relation is attributable to the blockade of the channel by intracellular Mg2+ and/or Na+.
Potassium currents evoked by brief depolarizations in bull‐frog sympathetic ganglion cells.
Authors: Lancaster B , Pennefather P
Published: December 2014

1. Sympathetic neurones of the bull‐frog Rana catesbeiana were subjected to a two‐electrode voltage‐clamp technique in order to investigate the K+ currents which can be elicited by action potentials or similar brief depolarizations. 2. Four separate K+ currents were observed (IC, IK, IAHP and IM). These could be separated on the basis of voltage sensitivity, Ca2+ dependence and deactivation kinetics. 3. Two of these currents, which were clearly activated by an action potential, were Ca2+ dependent. A voltage‐ and TEA (tetraethylammonium)‐sensitive K+ current, IC, was activated within the first 1‐2 ms of a depolarizing command. This current decayed on average with a time constant of 2.4 ms at ‐40 mV. The maximal conductance was outside the range which could be adequately voltage clamped but, as much as 2 muS could be activated by brief (2‐3 ms) commands. Activation of IC during an action potential accounts for the Ca2+ dependence of the repolarization. IC did not exhibit a transient component. 4. A second Ca2+‐dependent K+ current, IAHP, was also activated after as little as 1 ms depolarization but was not voltage sensitive and was much less sensitive to TEA. The current decayed with a time constant of around 150 ms at ‐40 mV. The maximal conductance was about 30 nS. 5. The voltage‐sensitive delayed rectifying current, IK, made a contribution to the total K+ conductance of the cell similar to IC in magnitude; however, the current is not activated within the normal voltage range or time course of an action potential. The current decayed on average with a time constant of 21 ms at ‐40 mV. 6. IM, a muscarine‐ and voltage‐sensitive current, is not activated to any significant degree by a single action potential. The data further imply that the rate of opening of the ion channels mediating IM is less voltage sensitive than the rate of closing. 7. Large changes in the K+ reversal potential occur following depolarizing commands which evoke large K+ currents. This is attributed to K+ accumulation within a restricted extracellular space. Extracellular K+ may double or even triple during a single action potential.
Spinal inhibition of phrenic motoneurones by stimulation of afferents from leg muscle in the cat: blockade by strychnine.
Authors: Eldridge F L , Millhorn D E , Waldrop T
Published: December 2014

1. Phrenic nerve responses to stimulation of calf muscle receptors or their afferents were studied in paralysed high (C1) spinal cats whose phrenic nerve activity was evoked by activation of the intercostal‐to‐phrenic reflex. End‐tidal PCO2 was maintained at a constant level by means of a servo‐controlled ventilator. 2. Physical stimulation of calf muscles or electrical stimulation of the tibial nerve uniformly caused inhibition of phrenic activity evoked by facilitatory conditioning stimuli. The degree of inhibition gradually decreased as muscle stimulation continued, and there was a post‐stimulus augmentation of phrenic activity. 3. Pre‐treatment with subconvulsive doses of strychnine, an antagonist of the neurotransmitter glycine, partially or completely blocked the inhibitory effects on phrenic activity of muscle‐afferent stimulation. The blockade was reversible with time. 4. Pre‐treatment with a subconvulsive dose of bicuculline, an antagonist of the neurotransmitter gamma‐aminobutyric acid (GABA), had no effect on the inhibitory mechanism. 5. We conclude that glycine is an important transmitter of the inhibition of phrenic motoneurones induced by muscle‐afferent stimulation, but that GABA is not involved in this inhibitory mechanism.
Reciprocal Ia inhibition between ankle flexors and extensors in man.
Authors: Crone C , Hultborn H , Jespersen B , Nielsen J
Published: December 2014

1. Reciprocal inhibition between antagonist muscle groups at the ankle has been investigated in sixty healthy subjects. Hoffmann reflexes (H reflexes) in the soleus and tibialis anterior muscles were used to assess changes in reciprocal inhibition evoked by electrical stimulation of antagonist muscle nerves. 2. Inhibition of the soleus H reflex was evoked by a single conditioning stimulus to the common peroneal nerve, and inhibition of the tibialis anterior H reflex was elicited by one conditioning stimulus to the posterior tibial nerve. Symmetrical central connections between the antagonist flexors and extensors were assumed and under this assumption the central delay for the inhibition, in addition to the delay for monosynaptic Ia excitation, was calculated to be about 1 ms. The inhibition was evoked by weak stimuli to the nerves from antagonist muscle groups; the threshold for the inhibition was around 0.6 X threshold for a direct motor response (M‐threshold). Furthermore, tendon taps to the Achilles tendon facilitated the soleus H reflex and inhibited the tibialis anterior reflex at short latencies. The short central delay, the low electrical threshold and the.actions of Achilles tendon taps strongly suggest that the early reciprocal inhibition is homologous to the disynaptic Ia inhibition previously studied in animal experiments. 3. With the test soleus H reflex kept at 15‐25% of the maximum directly evoked motor response (M‐response) and the strength of the conditioning peroneal nerve stimulation kept at 1.0 X M‐threshold, the inhibition from the peroneal nerve ranged between 0 and 40% (mean, 14.9%) at rest. 4. Changes in the amount of reciprocal inhibition from the peroneal nerve were studied both during tonic and dynamic dorsi‐ and plantarflexion. During tonic dorsiflexion there was no significant change of inhibition as compared to rest, while inhibition decreased during tonic plantarflexion. However, during ramp‐and‐hold dorsiflexion there was a transient increase in reciprocal inhibition of the soleus H reflex. This increase in inhibition from the peroneal nerve could be seen 50 ms prior to the onset of contraction. The increase in inhibition before and at the very beginning of the contraction cannot be due to sensory feed‐back during contraction, but must depend on a supraspinal control of the spinal cord. 5. At conditioning‐test intervals of 4‐6 ms, the inhibition of the soleus H reflex from the peroneal nerve was considerably larger during tonic dorsiflexion than at rest. Thus, tonic dorsiflexion revealed an inhibition with long latency from the peroneal nerve, which was not seen at rest.(ABSTRACT TRUNCATED AT 400 WORDS)
Properties of two calcium‐activated hyperpolarizations in rat hippocampal neurones.
Authors: Lancaster B , Nicoll R A
Published: December 2014

1. Intracellular recording from hippocampal CA1 pyramidal cells in the slice preparation was used to analyse the pharmacological sensitivity of action potential repolarization and the hyperpolarizations that follow the action potential. The Ca2+‐activated after‐hyperpolarizations (a.h.p.s) could be divided into a fast a.h.p. with a time course of milliseconds, and a slow a.h.p. which lasted for a few seconds at a temperature of 30 degrees C. 2. The repolarization of the action potential is sensitive to the Ca2+ channel blocker Cd2+. This effect is simultaneous with a block of the fast a.h.p. which follows immediately upon the repolarization of the action potential. The slow a.h.p. was also blocked by Cd2+. 3. Low concentrations of the K+ channel blocker, tetraethylammonium (TEA; 200‐500 microM), block the fast a.h.p. and slow down action potential repolarization. The slow a.h.p. was not affected by low concentrations of TEA. 4. The action potential repolarization and the fast a.h.p. are also reversibly sensitive to charybdotoxin. This agent had no effect on the slow a.h.p. 5. When EGTA or BAPTA were added to the normal recording electrolyte (KMeSO4), the generation of slow a.h.p.s was prevented. In addition, cells impaled with BAPTA‐containing electrodes displayed broader action potentials and much reduced fast a.h.p.s compared to recordings made with electrodes containing KMeSO4 alone or with EGTA. 6. The slow a.h.p. can be eliminated by noradrenaline, 8‐bromocyclic AMP or carbachol. Under these conditions there are no effects on the fast a.h.p. or on action potential duration. 7. Block of the fast a.h.p. with TEA or CTX (charybdotoxin) is associated with an increased frequency of the first few action potentials during a depolarization. This is a quite distinct effect from the greatly increased number of action potentials which results from block of the slow a.h.p. 8. The results support a conclusion that the fast a.h.p. is generated by the TEA‐ and voltage‐sensitive Ca2+‐activated K+ current, IC. This current is involved in spike repolarization and turns off upon the return to resting potential. Thus block of IC has no effect on the slow a.h.p. which is caused by a separate membrane current.
An intrinsic potential‐dependent inactivation mechanism associated with calcium channels in guinea‐pig myocytes.
Authors: Hadley R W , Hume J R
Published: December 2014

1. Currents through Ca2+ channels of single guinea‐pig ventricular myocytes were studied using patch electrodes for whole‐cell recording. Currents through Na+ and K+ channels were suppressed by the application of drugs or the substitution of impermeant ions. 2. Inactivation of the Ca2+ current (ICa) was investigated using a two‐pulse protocol. The amount of inactivation left behind by a pre‐pulse appeared to be related to current magnitude, as others have reported. The dependence of inactivation on the pre‐pulse potential was partially U‐shaped, as the amount of inactivation peaked at 0 mV and then declined with more positive pre‐pulses. 3. Non‐specific current carried by monovalent ions through Ca2+ channels (Ins) was induced by lowering the extracellular Ca2+ concentration with EGTA. Ins peaked in an inward direction at ‐20 mV, reversed direction at +22 mV, and became a large outward current at more positive potentials. 4. Ins inactivated with a slow time course. The inactivation was not due to accumulation or depletion phenomena. Studies using two‐pulse protocols showed that the amount of inactivation left by a pre‐pulse was directly related to the pre‐pulse potential. 5. The addition of micromolar amounts of free Ca2+ to the external solution induced outward rectification of Ins. Inward currents were small or absent, while larger outward currents could still be seen at very positive potentials. Ca2+‐channel inactivation still occurred under these conditions, even in the absence of any significant ionic movement. 6. The time courses of Ins inactivation and recovery were studied. The half‐time of Ins inactivation decreased with larger depolarizations. Recovery of Ins was very slow, but could be accounted for by changes in the surface charge of the membrane. 7. It is concluded that Ins inactivation is due solely to a voltage‐dependent inactivation process which is intrinsic to myocardial Ca2+ channels. Voltage‐dependent inactivation appears to account for a significant proportion of total Ca2+‐channel inactivation at negative potentials, and appears to account for almost all of the inactivation at very positive potentials, even in the presence of millimolar concentration of external Ca2+.
Two types of acetylcholine receptor channels in developing Xenopus muscle cells in culture: further kinetic analyses.
Authors: Igusa Y , Kidokoro Y
Published: December 2014

1. Further developmental changes in acetylcholine (ACh) receptor channel function were examined in Xenopus muscle cultures using the cell‐attached patch‐clamp technique. 2. Two types of acetylcholine (ACh) receptor channel events, low‐ and high‐conductance channel events, were distinguished as reported earlier. Apparent open‐time histograms for high‐conductance channel events were well fitted by a single exponential but those for low‐conductance channel events were sometimes fitted better by two exponentials. 3. In low‐conductance channel events when the open‐time histogram was well fitted by two exponentials, successive open times were correlated: an event with a long open time tended to be followed after a brief interval (less than 1 ms) by another long‐duration event. A short‐duration event was less frequently followed by an event within a short interval (1 ms) with a long‐duration event. 4. Closed‐time histograms for the interval between successive low‐conductance channel events and between successive high‐conductance channel events were both fitted by two exponentials. The fast time constant was 0.36 ms for the high‐conductance channel event and 0.31 ms for the low‐conductance channel event. There was an indication that a third and faster component was hidden in the first bin (0‐200 microseconds) in the closed‐time histogram of both types of channel events. 5. Defining a burst as successive openings separated by closures briefer than 1 ms, the number of gaps per burst was different for the two types of channel events. They were 0.16 for high‐ and 0.37 for low‐conductance channel events. In both types of channels, neither the fast component in the closed‐time histogram nor the number of gaps per burst changed with time in culture. 6. The apparent open time of both types of channels increased progressively as ACh concentration was increased, suggesting an increasing number of unresolved closures at higher concentrations. At 100 microM‐ACh the apparent open time became shorter probably due to channel blockade by ACh molecules. Closed‐time histograms were fitted by two exponentials. The time constant of the fast component remained similar to that at low concentration (0.2 microM) up to 20 microM, but the relative number of closures belonging to this component increased with ACh concentration. In contrast, the slow component shortened its time constant as ACh concentration increased and the relative frequency decreased. Again, there was an indication that another faster component existed in the closed‐time histogram.(ABSTRACT TRUNCATED AT 400 WORDS)
Differences in the amplitude of X‐cell responses as a function of depth in layer A of lateral geniculate nucleus in cat.
Authors: Bowling D B , Wieniawa-Narkiewicz E
Published: December 2014

1. Extracellular recordings were made from 131 X‐like cells (hereafter called X cells) at different depths in layer A of the lateral geniculate nucleus (l.g.n.) in the cat. The depths of the cells were measured accurately by orienting the electrodes parallel to the borders of the layer and reconstructing the electrode tracks from histological sections. 2. Each cell was stimulated with a standardized stimulus; a 500 ms, low‐contrast (10%) spot of light, matched in size to the centres of the receptive fields. The responses were later compared with the depths of the cells in the layer. 3. The amplitudes of the responses, which ranged between peak values of 20 and 400 spikes/s in different cells, were related to the depths of the cells in the layer. On average, the response amplitudes of the X‐on cells near the borders of the layer were small compared to those in the middle. The responses of the X‐off cells were reciprocal; large near the borders of the layer and small in the middle. 4. The results reveal a sublaminar organization in layer A based on the signs and amplitudes of X‐cell responses. It is suggested that the pattern reflects differences in signalling within the X‐on and X‐off channels that are preserved in the relay to the visual cortex.
Human muscle strength training: the effects of three different regimens and the nature of the resultant changes.
Authors: Jones D A , Rutherford O M
Published: December 2014

1. Increases in strength and size of the quadriceps muscle have been compared during 12 weeks of either isometric or dynamic strength training. 2. Isometric training of one leg resulted in a significant increase in force (35 +/‐ 19%, mean +/‐ S.D., n = 6) with no change in the contralateral untrained control leg. 3. Quadriceps cross‐sectional area was measured from mid‐thigh X‐ray computerized tomography (c.t.) scans before and after training. The increase in area (5 +/‐ 4.6%, mean +/‐ S.D., n = 6) was smaller than, and not correlated with, the increase in strength. 4. The possibility that the stimulus for gain in strength is the high force developed in the muscle was examined by comparing two training regimes, one where the muscle shortened (concentric) and the other where the muscle was stretched (eccentric) during the training exercise. Forces generated during eccentric training were 45% higher than during concentric training. 5. Similar changes in strength and muscle cross‐sectional area were found after the two forms of exercise. Eccentric exercise increased isometric force by 11 +/‐ 3.6% (mean +/‐ S.D., n = 6), and concentric training by 15 +/‐ 8.0% (mean +/‐ S.D., n = 6). In both cases there was an approximate 5% increase in cross‐sectional area. 6. It is concluded that as a result of strength training the main change in the first 12 weeks is an increase in the force generated per unit cross‐sectional area of muscle. The stimulus for this is unknown but comparison of the effects of eccentric and concentric training suggest it is unlikely to be solely mechanical stress or metabolic fluxes in the muscle.
Arterial supply, venous drainage and collateral circulation in the nose of the anaesthetized dog.
Authors: Lung M A , Wang J C
Published: December 2014

1. In pentobarbitone‐anaesthetized dogs, nasal blood flows were measured with electromagnetic flow sensors. 2. The terminal internal maxillary artery was found to supply 22 +/‐ 2.2 ml min‐1 (one side) to the nasal mucosa via the sphenopalatine and major palatine branches; the artery was found to receive multiple supply routes from common carotid, vertebral and subclavian arteries. 3. Nasal mucosa was found to receive collateral flow from contralateral terminal internal maxillary artery (about 5 to 10% of normal flow) and branches of subclavian arteries (about 36% of normal flow). 4. Nasal mucosa was found to have two venous systems: the low‐flow (12 +/‐ 1.0 ml min‐1; both sides) and low‐pressure (7 +/‐ 0.6 mmHg) sphenopalatine veins draining the posterior nasal cavity and the high‐flow (30 +/‐ 1.4 ml min‐1; both sides) and high‐pressure (17 +/‐ 1.0 mmHg) dorsal nasal veins draining the anterior nasal cavity. 5. PO2 of nasal venous blood was found to range from 62 +/‐ 2.9 mmHg to 65 +/‐ 3.4 mmHg. During nitrogen challenge to the nose, the sphenopalatine venous PO2 dropped to 35 +/‐ 3.0 mmHg while the dorsal nasal venous PO2 remained unchanged, suggesting that the sphenopalatine veins were responsible for draining capillary flow and dorsal nasal veins arteriovenous anastomotic flow as well. 6. Microscopic examination of the vascular casts confirmed that arteriovenous anastomoses were located only in the anterior nasal cavity.
Effects of ischaemia upon reflex electromyographic responses evoked by stretch and vibration in human wrist flexor muscles.
Authors: Cody F W , Goodwin C N , Richardson H C
Published: December 2014

1. The reflex electromyographic responses evoked in a wrist flexor muscle, flexor carpi radialis (f.c.r.), by forcible extension of the wrist ('stretch') and by vibration of the flexor tendon have been studied in normal subjects. Reflexes were elicited during the maintenance of a low level of voluntary flexor contraction (5% maximum). Stretch regularly produced a relatively prolonged (ca. 100 ms duration) increase in e.m.g. activity which was usually divisible into short‐latency (ca. 25 ms, M1) and long‐latency (ca. 50 ms, M2) peaks. Vibration produced a single, phasic peak, at short latency, with no sign of an accompanying long‐latency wave comparable to the M2 stretch response. 2. Ischaemia was induced by inflation of a blood‐pressure cuff around the upper arm and its effects upon the reflex patterns were studied. During ischaemia M1 stretch responses showed a more rapid and pronounced decline than did M2 responses and were abolished before voluntary power was appreciably affected. Vibration‐evoked short‐latency peaks changed in an essentially parallel manner to M1 stretch reflexes. During recovery from ischaemia M2 reflexes were restored before short‐latency responses. 3. The patterns of reflex reductions in e.m.g. upon withdrawal of stimulation were also studied. Such troughs in activity, under non‐ischaemic conditions, regularly commenced at short latency and were of relatively small amplitude. The records of several of the subjects, and particularly ones obtained during ischaemia, suggested that release of stretch (with concomitant stretch of antagonists) could elicit an additive, long‐latency decline in e.m.g. The existence of any such separate, delayed component was never observed upon termination of vibration. 4. Measurements of changes in the latencies and durations of reflex components, accompanying the progression of ischaemia, indicated that depression of early reflex activity resulted in part from increases in the latencies of these initial peaks but predominantly reflected simultaneous and separate reductions in their amplitudes. 5. The generation of short‐latency reflexes by stretch and vibration, both of which stimuli powerfully excite muscle spindle primary endings, and the marked susceptibility of these responses to ischaemia supports their being mediated by group Ia afferents. The contrasting behaviour of M2 stretch responses, both regarding their absence with vibration and their resistance to ischaemia, suggests that they depend crucially upon a separate group of reflex afferents.(ABSTRACT TRUNCATED AT 400 WORDS)
Caesium ions activate chloride channels in rat cultured spinal cord neurones.
Authors: Hughes D , McBurney R N , Smith S M , Zorec R
Published: December 2014

1. Caesium ions (Cs+), applied extracellularly, caused a decrease in the input resistance of cultured spinal cord (s.c.) neurones and depolarized the neurones when they contained 140 mM‐CsCl. 2. The reversal potential for Cs+‐activated currents shifted 56 mV on average for a 10‐fold reduction in the intracellular chloride ion (Cl‐) activity, indicating that the Cs+‐activated currents were specific to Cl‐. 3. The activation of Cl‐ currents by Cs+ was not due to the depolarization‐evoked release of neurotransmitter from presynaptic terminals. We therefore suggest that Cs+ were acting directly on the extracellular surface of the s.c. neurones to activate Cl‐ currents. 4. Cs+‐activated currents showed desensitization in the presence of 140 mM‐Cs+. 5. The log‐log plot of the dose‐response data could be fitted with a straight line with a slope of 1.7 +/‐ 0.4 (n = 6), indicating that at least 2 Cs+ were needed to activate a single Cl‐ channel. The KD of the Cs+‐induced response was greater than 69 mM. 6. In outside‐out patches Cs+ activated single Cl‐ channels. These channels were not activated by sodium or potassium ions. 7. The Cs+‐activated channels displayed a total of five distinct conductance states which had mean conductances of 20, 30, 43, 66 and 92 pS. The 30 and 43 pS states were the most frequently occurring states. 8. The conductance states of the Cs+‐activated channel have the same conductances as those reported for gamma‐aminobutyric acid (GABA)‐ and glycine‐activated channels in rat s.c. neurones. We therefore conclude that Cs+ activate the same type of Cl‐ channel as GABA and glycine through an unidentified receptor.