bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of the hyperpolarization‐activated current (if) induced by acetylcholine in rabbit sino‐atrial node myocytes.
Authors: DiFrancesco D , Tromba C
Published: December 2014

1. The action of acetylcholine (ACh) on the hyperpolarization‐activated ('pacemaker') current if was studied in single myocytes from the sino‐atrial (SA) node region of the rabbit heart, where low doses of ACh slow spontaneous activity by prolonging the diastolic depolarization phase. 2. Besides activating an outward component at voltages positive to the K+ equilibrium potential (iK,ACh), ACh depressed the current if activated on hyperpolarization at concentrations in the range 0.03‐1 microM. 3. The ACh‐dependent if depression was dissected from modifications of iK,ACh by blocking iK,ACh with barium and was studied under conditions that minimized the interference of other current changes caused by ACh. 4. The study of if modification by ACh with three‐pulse protocols and the measurement of fully activated I‐V relations of if with and without ACh revealed that ACh acted on if by shifting the current activation range to more negative voltages, with no obvious alteration of the fully activated current amplitude. 5. The action of ACh on if was opposite to that caused by catecholamines. The presence of isoprenaline (IP) did not prevent ACh inhibition of if, nor did the presence of ACh prevent the if stimulation caused by IP. The effects of IP and ACh on if were additive. 6. The ACh‐induced inhibition of if was reversed by addition of atropine and could be mimicked by muscarine, indicating that muscarinic receptors mediate it. The implications of these findings on the regulation of pacemaker activity by ACh is discussed.
Inhibition of neurones transmitting non‐monosynaptic Ia excitation to human wrist flexor motoneurones.
Authors: Malmgren K , Pierrot‐Deseilligny E
Published: December 2014

1. The possibility was investigated that the transmission of the interneuronally mediated Ia excitation to wrist flexor motoneurones described in the companion paper is inhibited by stimulation of afferent fibres. Two techniques were used: (i) the post‐stimulus time histogram (PSTH) method for studying changes in firing probability of individual voluntarily activated wrist flexor motor units following various peripheral stimulations; and (ii) the indirect technique of spatial facilitation of the H reflex. 2. In those individual units where stimulation of the median and/or the ulnar nerve evoked a non‐monosynaptic excitation, this excitation was reduced when the afferent input was increased. This reduction of the non‐monosynaptic Ia excitation was found in 80% of the motor unit recordings, whether the afferent input was increased by increasing the stimulus intensity to one nerve or by using combined stimulation of two nerves. 3. Both group I muscle and low‐threshold cutaneous afferents were shown to be able to reduce the non‐monosynaptic Ia excitation. 4. The onset of the depression of the excitation was always found within the same 1 ms bin as that of the excitation. 5. Whatever the amount of afferent input (stimulus intensity increased up to motor threshold, spatial and temporal summation, summation of inhibitory effects from different origins), the depression could at the very most suppress the non‐monosynaptic Ia excitation: i.e. a trough in the PSTH, reflecting an inhibition at the motoneuronal level, never appeared. In those units in which there was not non‐monosynaptic excitation, peripheral stimulation did not evoke any inhibition appearing as a trough in the PSTH either. Hence, inhibition only appeared when there was a non‐monosynaptic excitation, and then as a depression of it. 6. On the basis of these findings it is argued that the inhibition is not exerted directly onto motoneurones but acts at a pre‐motoneuronal level on the interneurones mediating the non‐monosynaptic Ia excitation to motoneurones. 7. Similarly, the homonymous non‐monosynaptic Ia facilitation of the flexor carpi radialis H reflex was shown to be reduced by a preceding stimulation applied to the ulnar nerve. It is argued that this result is also compatible with an inhibition of transmission in interneuronal excitatory pathways to motoneurones. 8. It is suggested that the non‐monosynaptic excitation of wrist flexor motoneurones in man and the inhibition of this excitation, both evoked by stimulation of low‐threshold afferents, could be mediated through a system of cervical propriospinal neurones. Some aspects of the possible role of this system during movement are discussed.
The peripheral‐chemoreceptor threshold to carbon dioxide in man.
Authors: Duffin J , McAvoy G V
Published: December 2014

1. The threshold of the ventilatory response to carbon dioxide mediated by the peripheral chemoreceptors was determined under mild hypoxic conditions during both rest and exercise in eight volunteers. 2. The method used was an adaptation of the Read rebreathing technique, modified for hypoxia and with prior hyperventilation. The method produced values of ventilation and carbon dioxide which, when plotted against each other, exhibited three straight‐line segments of differing slopes. The break‐points were interpreted as the resting peripheral‐ and central‐chemoreceptor thresholds. 3. Similar plots of exercise ventilation and carbon dioxide were used to determine the peripheral‐chemoreceptor threshold during exercise. However, the points for these plots were obtained from a number of separate rebreathing experiments in such a way as to avoid the divergence between the carbon dioxide levels as measured at the mouth and those at the site of the central chemoreceptors, which would normally occur during rebreathing in exercise. 4. During the course of rebreathing experiments similar to those done at rest, mild treadmill exercise was begun abruptly. The ventilation measured at the third breath of exercise was plotted against the level of carbon dioxide at which the exercise started. In this way, each such rebreathing experiment provided a single point for the plot of ventilation against carbon dioxide in exercise. 5. The results showed that the threshold of the ventilatory response to carbon dioxide mediated by the peripheral chemoreceptors was approximately 39 mmHg (5.2 kPa) while that for the central chemoreceptors was approximately 45 mmHg (6.0 kPa). Neither the peripheral‐chemoreceptor threshold, nor the peripheral‐chemoreceptor sensitivity to carbon dioxide was changed at the start of exercise.
Multiple actions of adenosine 5'‐triphosphate on chick skeletal muscle.
Authors: Hume R I , Thomas S A
Published: December 2014

1. Extracellularly applied adenosine 5'‐triphosphate (ATP) is known to have an excitatory action on chick skeletal muscle. By making intracellular recordings from cultured chick myotubes bathed with blockers of several types of voltage‐dependent channels, the direct action of ATP could be observed. 2. When muscle cells were studied near their resting potential, ATP usually produced a biphasic response. There was a rapid initial depolarization, followed by a slower repolarization. The repolarization could drive cells negative to their initial resting potential, indicating that it was not due simply to desensitization of the process that produced the depolarization. Thus there are at least two distinct responses to ATP. 3. At room temperature the early response to ATP activated within 20 ms, and the second response activated with a latency of approximately 1 s. In our standard blocking solution, the average reversal potential of the early response was ‐17 mV, while the late response had a reversal potential that was negative to ‐70 mV. In a few cells the second response appeared to be absent. 4. The amplitude and time course of the late response were substantially decreased by low temperature (12 degrees C) and increased by high temperature (37 degrees C). In contrast, temperature had much smaller effects on the early response. Both the time course and temperature dependence of the late response suggest that an intracellular second messenger system may be involved in its activation. 5. Ion‐substitution experiments were performed to determine the type of conductance changes that evoke each response. These indicated that the early response was due to an increased membrane permeability to sodium, potassium and chloride, but not to large cations or anions, and that the late response was due to an increased permeability to potassium. 6. Measurement of the responses of muscle cells to acetylcholine supported the conclusion that both anions and cations are permeable during the early ATP response. Under conditions in which there was a large negative reversal potential for all cations, and a large positive reversal potential for all anions, the early ATP response reversed approximately 50 mV positive to the acetylcholine response. 8. The possibility that the early ATP response is due to a channel selective for size, but not charge, is discussed.
Long‐latency stretch reflexes as co‐ordinated functional responses in man.
Authors: Gielen C C , Ramaekers L , van Zuylen E J
Published: December 2014

1. Reflex activity in human arm muscles has been measured in response to torque perturbations around the elbow joint in the flexion‐extension direction and/or the supination‐pronation direction. Intramuscular fine‐wire electrodes were used to record electromyographic (EMG) activity in the muscles. A pre‐load was applied in the same direction as or in a different direction to the perturbation. The subjects were instructed to ‘hold on’, which means that they had to actively resist the perturbation without unduly co‐activating their muscles. 2. The EMG activity showed segmented reflex responses with short‐latency (25‐50 ms) and long‐latency (50‐75 ms) components, followed by other bursts of activity which probably originated from the subject's voluntary or triggered reactions. 3. Motor units in m. triceps gave short‐latency and long‐latency responses to imposed elbow extension but only long‐latency responses were seen to imposed pronation, which does not stretch m. triceps. Motor units in m. brachialis gave short‐latency and long‐latency excitatory (inhibitory) responses to imposed extension (flexion) torques. However, only long‐latency inhibitory responses were observed to imposed pronation torques. Motor units in m. biceps gave short‐latency and long‐latency excitatory responses to imposed pronation torques. 4. These results show that the long‐latency reflex cannot be the result of a simple feed‐back mechanism that controls muscle length only. We argue that the long‐latency reflex activity reflects the co‐ordinated activation of muscles which is necessary for an adequate response. This hypothesis is supported by the fact that the distribution of long‐latency reflex activity over muscles was found to be similar to the distribution of activation found during a voluntary exerted torque in the direction opposite to the applied perturbation.
Electrophysiological properties of rostral medullary respiratory neurones in the cat: an intracellular study.
Authors: Bianchi A L , Grélot L , Iscoe S , Remmers J E
Published: December 2014

1. We recorded the membrane potentials of sixty‐three respiratory neurones in the rostral, ventral medulla of decerebrate vagotomized cats. Stable recordings were obtained in thirty‐eight expiratory and twenty‐five inspiratory neurones. Axonal projections were identified by antidromic invasion after electrical stimulation of the region of the dorsal respiratory group (DRG), spinal cord, and the cervical vagus, superior laryngeal and pharyngeal nerves. 2. Two types of expiratory neurones were encountered: those in which the membrane potential progressively depolarized (augmenting neurons, n = 22) and those in which the membrane potential repolarized (decrementing or post‐inspiratory neurones, n = 16) during the interval between phrenic bursts. Both types were hyperpolarized during inspiration by chloride‐dependent, inhibitory postsynaptic potentials (IPSPs) which decreased membrane resistance. In augmenting neurones two waves of IPSPs appeared, one early and one late in inspiration. 3. Five out of seventeen augmenting expiratory neurones tested were antidromically activated by contralateral stimulation of the spinal cord (n = 3) or the DRG (n = 2). Spinal axons were not detected in any of the sixteen decrementing expiratory neurones tested. Of thirteen expiratory neurones tested with pharyngeal nerve stimulation, one (an augmenting type) was antidromically activated. Superior laryngeal or vagal axons could not be demonstrated for any expiratory neurones. 4. Two types of inspiratory neurones were also encountered: those displaying progressive depolarization throughout inspiration (n = 5) and those which gradually repolarized after maximal depolarization at the onset of inspiration (n = 10). None of the former had identifiable spinal or medullary axons, but superior laryngeal axons were demonstrated in three and pharyngeal axons were found in three. None of the latter was antidromically activated from any of the sites stimulated. 5. Stimulation of the superior laryngeal or pharyngeal nerves evoked excitatory postsynaptic potentials (EPSPs) in all neurones except in post‐inspiratory neurones. In these, stimulation of the superior laryngeal or pharyngeal nerves evoked IPSPs in five of twelve neurones tested. 6. We conclude that a spectrum of respiratory neurones lie within or ventral to the retrofacial nucleus. These neurones may control upper‐airway muscles or may play a role in chemoreception.
The effect of thyroidectomy in the fetal sheep on lung liquid reabsorption induced by adrenaline or cyclic AMP.
Authors: Barker P M , Brown M J , Ramsden C A , Strang L B , Walters D V
Published: December 2014

1. In fetal sheep at 113‐120 days' gestation, thyroidectomy was performed and tracheal, arterial and venous catheters inserted. Following a recovery period experiments were performed from 120‐145 days to measure changes in lung liquid secretion or its absorption in response to I.V. adrenaline infusion or to introduction of dibuteryl cyclic AMP into lung liquid. The results were compared with those previously obtained in non‐thyroidectomized fetuses. 2. Plasma levels of thyroid hormones in non‐thyroidectomized fetuses confirmed the pattern found by previous workers. In thyroidectomized fetuses the levels of thyroxine (T4), tri‐iodothyronine (T3) and reverse T3 (rT3) were very low except in one fetus which showed biochemical evidence of thyroid regeneration towards the end of gestation. 3. In thyroidectomized fetuses the normal response to adrenaline infusion (diminution of reversal of lung liquid secretion) was profoundly suppressed and very little gestational maturation in this response took place, except in the one fetus with evidence of thyroid regeneration in which a normal reabsorptive response developed in late gestation. 4. In thyroidectomized fetuses, the normal response to dibuteryl cyclic AMP was greatly reduced and its increase with gestation which normally parallels that seen during adrenaline infusion did not take place.
Permeation of barium and cadmium through slowly inactivating calcium channels in cat sensory neurones.
Authors: Taylor W R
Published: December 2014

1. Instantaneous current‐voltage (I‐V) relations were measured from tail currents with 10 mM‐external calcium at 20 degrees C. The I‐V relations had a lower potential dependence than predicted by the Goldman‐Hodgkin‐Katz constant‐field equation. Previously proposed symmetric two‐site three‐barrier (2S3B) rate theory models were able to account for the I‐V relations reasonably well. 2. Reversal of the current flow through the calcium channels was recorded using 10 mM‐barium internally and 20 mM‐barium externally. The channels appeared to rectify at positive potentials, a property not consistent with symmetric rate theory models. 3. Externally applied cadmium ions blocked the calcium channels through at least two sites. One high‐affinity blocking site was located within the membrane electric field and had a dissociation constant of around 16 microM at O mV. Cadmium block at this site was relieved with hyperpolarization with a voltage dependence equivalent to a divalent cation moving through about 75% of the membrane electric field. 4. A low‐affinity potential‐independent blocking site also appeared to be present, having a dissociation constant of around 106 microM. 5. Cadmium had significant effects on the tail current kinetics at potentials close to 0 mV, presumably due to slow unblocking events. The rate at which cadmium ions left the calcium channel free to conduct was estimated to be about 3300 s‐1 at +10 mV.
Calcium concentration in the myoplasm of skinned ferret ventricular muscle following changes in muscle length.
Authors: Allen D G , Kentish J C
Published: December 2014

1. Ferret ventricular muscles were skinned by prolonged application of Triton X‐100. Aequorin was allowed to diffuse into the myoplasmic space and the resulting light emission was used to monitor the myoplasmic [Ca2+]. The muscle was then activated with a lightly buffered Ca2+ solution and the changes in myoplasmic [Ca2+] and tension in response to length changes were investigated. 2. A sudden reduction in muscle length led to a rapid increase in myoplasmic [Ca2+] to a new level which was maintained as long as muscle length was reduced and which was reversed when the muscle was stretched back to the control length. The rate of increase of [Ca2+] when the muscle length was reduced was greater than the rate of decrease in [Ca2+] when the muscle was stretched. 3. Increasing the concentration of EGTA in the activating solution, so as to increase its Ca2+‐buffering capacity, eliminated the changes in myoplasmic [Ca2+] in response to a length change but had little effect on developed tension. 4. On stretching the muscle there was a slow component of recovery of tension with a time course broadly similar to the rate of decrease of myoplasmic [Ca2+]. The time course of tension redevelopment and of the accompanying reduction in myoplasmic [Ca2+] both decreased to a similar extent when the [Ca2+] used to activate the muscle was increased. 5. Step reductions of length of increasing amplitude caused increases in myoplasmic [Ca2+] which were larger in proportion to the size of the step. 6. Step reductions of length of equal size but from different starting lengths caused changes in myoplasmic [Ca2+] the amplitude of which correlated with the change in tension rather than the change in length. 7. The increase in myoplasmic [Ca2+] when muscle length is reduced suggests that Ca2+ is released from a site in the muscle, probably troponin C. The time course and magnitude of the changes in myoplasmic [Ca2+] correlate more closely with the changes in developed tension than muscle length.
The effect of stimulation of left atrial receptors on coronary blood flow in anaesthetized dogs.
Authors: Drinkhill M J , Kaye D , Mary D A
Published: December 2014

1. To determine whether stimulation of atrial receptors reflexly affects coronary blood flow, experiments were performed in seven dogs anaesthetized with alpha‐chloralose. The left upper and middle pulmonary vein‐atrial junctions and atrial appendage were stretched by distension of small balloons. Coronary blood flow was measured using an electromagnetic flowmeter positioned around the origin of the left anterior descending or circumflex coronary artery. 2. Following prevention of the reflex increase in heart rate by atrial pacing or propranolol, distension of the small balloons was shown to result in a decrease in mean coronary blood flow. 3. Cooling of the cervical vagosympathetic nerve trunks to 9 degrees C abolished the response of a decrease in mean coronary blood flow to distension of the balloons. 4. The response of a decrease in mean coronary blood flow was abolished by bretylium tosylate. 5. It was shown that a decrease in mean coronary blood flow occurred in response to stimulation of left atrial receptors, and that this decrease was reflex in nature. This reflex response is likely to involve atrial receptors discharging into afferent myelinated vagal fibres, and the efferent limb involves cardiac sympathetic pathways.
Unloading of tendon organ discharges by in‐series motor units in cat peroneal muscles.
Authors: Horcholle‐Bossavit G , Jami L , Petit J , Vejsada R , Zytnicki D
Published: December 2014

1. The discharges from individual Golgi tendon organs of peroneus tertius and brevis muscles were recorded in anaesthetized cats during the isometric contractions of single motor units. Upon combined contractions of several motor units, two sorts of unloading effects were observed. 2. First, the contraction of a motor unit which, by itself, was without action on a tendon organ could produce a reduction in the response of the receptor to one of its activating motor units. Unloading effects exerted by such in‐parallel motor units could effectively interfere with the actions of in‐series motor units on the receptor. 3. Second, the contraction of a motor unit activating a tendon organ could reduce the response of this tendon organ to the contraction of another of its activating units. This new type of unloading effect, exerted by in‐series motor units, was demonstrated by the fact that the simultaneous contraction of both units elicited less discharge from the receptor than the contraction of a single unit. 4. Unfused contractions of a fast‐type motor unit eliciting a response in which the tendon organ discharge was driven 1:1 at the frequency of stimulation of the motor unit, could exert unloading actions on the response of the receptor to another motor unit eliciting a higher discharge frequency. 5. In‐series unloading actions were exerted not only by fast‐type motor units developing large forces, but also by relatively small slow‐type motor units. 6. The high incidence of in‐parallel and in‐series unloading effects suggests that their consequences may be functionally significant. When large numbers of motor units are being recruited in a muscle, unloading effects might result in a limitation of the Ib afferent discharges from this muscle, preventing an excessive increase of autogenetic inhibition.
The effect of anions on bound acetylcholine in frog sartorius muscle.
Authors: Ceccarelli B , Molenaar P C , Oen B S , Polak R L , Torri‐Tarelli F , van Kempen G T
Published: December 2014

1. Frog sartorius muscles were treated with an irreversible cholinesterase inhibitor and then incubated in isotonic potassium propionate solution (isotonic KPr). Total and bound, presumably vesicular, acetylcholine (ACh) in the tissue and ACh in the medium were assayed by mass fragmentography, miniature end‐plate potentials (MEPPs) were recorded and the end‐plates were investigated by electron microscopy. 2. Incubation in isotonic KPr for 30 min stimulated ACh release and concomitantly decreased total and bound ACh. Nerve stimulation for 30 min by trains of impulses (0.1 s trains of 100 Hz, 1 train s‐1) in normal‐potassium propionate‐containing solution had the same effects. 3. When the tissue was incubated in normal‐K+ Ringer solution for 3 h, following chemical or electric stimulation, bound ACh recovered to about 75% of the initial value, provided that Cl‐ ions were present in the medium. In the presence of propionate instead of Cl‐ ions almost no recovery of bound ACh took place. There was also recovery of bound ACh in the presence of either NO3‐ or gluconate ions. In NO3‐ it was the same as in Cl‐, but in gluconate it was less than found in Cl‐ ‐containing medium. 4. Recovery of total ACh, in contrast to bound ACh, took place even in the presence of propionate ions, showing that extracellular Cl‐ is not required for the synthesis of ACh. 5. In terminals recovered in normal Ringer solution, many synaptic vesicles were found, but terminals ‘recovered’ in propionate solution were depleted of vesicles. 6. From these and other results it is concluded that the recycling of synaptic vesicles normally requires the presence of extracellular chloride.
Ventrolateral medullary neurones: effects on magnitude and rhythm of discharge of mesenteric and renal nerves in cats.
Authors: Stein R D , Weaver L C , Yardley C P
Published: December 2014

1. Discharge of whole mesenteric and renal nerves was recorded in eighteen chloralose‐anaesthetized, artificially respired cats. 2. Inhibition of tonic activity of neurones within the rostral ventrolateral medulla (RVLM blockade) by bilateral application of glycine caused significant reductions in discharge of renal and mesenteric nerves, arterial blood pressure and heart rate. The decrease in discharge of renal nerves was significantly greater than that of mesenteric nerves. 3. During the response to glycine application, the spinal cord was transected at the first cervical segment. The magnitude of renal nerve discharge after transection was not different from that during blockade of the RVLM. On the other hand, mesenteric nerve activity increased following spinal cord transection, returning to control levels. 4. Power spectral analysis revealed that mesenteric and renal nerves discharged with periodicities ranging from 1 to 6 Hz. Application of glycine to the RVLM reduced the slow rhythm in firing of mesenteric and renal nerves similarly. Transection of the spinal cord resulted in further reduction in the rhythmicity in discharge of both nerves. 5. The results indicate that excitatory drive from the RVLM is crucial for the maintenance of on‐going discharge of renal, but not of mesenteric nerves. However, such inputs are apparently essential to maintain the slow rhythm in firing of both nerves.
Enhancement of dopamine actions on rat nucleus accumbens neurones in vitro after methamphetamine pre‐treatment.
Authors: Higashi H , Inanaga K , Nishi S , Uchimura N
Published: December 2014

1. Intracellular recordings were made from the nucleus accumbens neurons in brain slices from rats previously treated with saline or methamphetamine. 2. In neurones from both methamphetamine‐ and saline (control)‐treated rats, dopamine (0.1 mM) produced three types of responses: a biphasic response consisting of an initial hyperpolarization followed by a depolarization, a monophasic hyperpolarization and a simple depolarization. 3. Haloperidol (1 microM) reversibly suppressed both responses to dopamine; (‐)‐sulpiride (1 microM) selectively abolished the depolarization and prolonged the hyperpolarization. Forskolin (10 microM) and dibutyryl adenosine 3',5'‐cyclic monophosphate (1 mM) mimicked the hyperpolarization. Both of the latter two substances were more effective in neurones from methamphetamine‐treated rats than in neurones from control rats. 4. In slices from methamphetamine‐treated rats, the dose‐response curve for the dopamine hyperpolarization was shifted to the left of that seen in neurones from control rats by a factor of approximately 100. The dose‐response curve for the dopamine depolarization was shifted to the right about 10‐fold in neurones from rats treated with methamphetamine. 5. In slices from control rats, dopamine (less than or equal to 0.1 mM) and methamphetamine (less than or equal to 1 microM) had no effect on the EPSPs evoked by focal electrical stimulation of the periaccumbens regions: dopamine (greater than or equal to 10 nM) and methamphetamine (1 microM) markedly depressed the EPSPs in slices from methamphetamine‐treated rats. Depolarizations evoked by application of exogenous glutamate were unaffected by dopamine (less than 5 microM). 6. In slices from methamphetamine‐treated rats, dopamine (greater than or equal to 10 nM), forskolin (greater than or equal to 1 microM) and dibutyryl adenosine 3',5'‐cyclic monophosphate (1 mM) depressed Ca2+‐dependent spikes as well as the EPSPs. Haloperidol (1 microM) completely reversed the depressions of the EPSPs and Ca2+‐dependent spikes by dopamine, while (‐)‐sulpiride (1 microM) was only partially effective. 7. These results indicate that chronic methamphetamine administration leads to enhancement of the actions of dopamine at D1 receptors located on glutamate and/or aspartate nerve terminals and of the dopamine hyperpolarization of principal neurones, which is also mediated by D1 receptors.
Cable properties of cat spinal motoneurones measured by combining voltage clamp, current clamp and intracellular staining.
Authors: Clements J D , Redman S J
Published: December 2014

1. Spinal alpha‐motoneurones were injected with horseradish peroxidase after measuring their voltage response to a brief current pulse and their current response to a small voltage step. 2. The morphology of each motoneurone was reconstructed from serial sections. The diameters and lengths of dendritic segments were used to build a compartmental model of each neurone's electrotonic structure. The specific resistivity of the membrane (Rm) was assumed to be constant throughout the dendrites, but it was lowered for the somatic membrane by the introduction of a somatic shunt resistance. 3. The specific resistances of the somatic and dendritic membrane were adjusted in the compartmental model until the responses of the model to the same current and voltage steps as those used in the experiment gave the best fits to the recorded transients. Satisfactory fits were obtained for six out of seven motoneurones. Dendritic Rm varied from 7 to 35 k omega cm2 and somatic Rm varied from 100 to 420 omega cm2. The dendritic Rm was 100‐300 times the somatic Rm for different neurones. 4. The calculated dendritic Rm was used to determine the geometric profile of the equivalent dendritic cable. This was found to be an approximately uniform cylinder for about 0.5 lambda and thereafter to taper rapidly to a final termination at 2‐3 lambda from the soma. 5. The results indicate that motoneurone dendrites are more electrically compact than was hitherto believed. The different Rm values for somatic and dendritic membrane, and the tapering of the dendritic cable, means that the cable model developed by Rall (1959, 1964) must be revised to take account of these spatial and electrical non‐uniformities.
Duodenal bulb control of the flow rate of digesta in the fasted and fed dog.
Authors: Malbert C H , Ruckebusch Y
Published: December 2014

1. Continuous measurement of the flow of digesta near the pylorus, and 5 cm aborally, was assessed in the conscious dog using a chronically implanted flowmeter. The patterns of flow were related to motor activity of the gastroduodenal junction. 2. Electromagnetic measurement of the flow was calibrated in vitro by means of a pulsatile pump. Validation was obtained in vivo by direct evaluation of the amount of chyme collected from an open duodenal cannula and indirectly by a dye‐dilution technique. 3. After a 12 h fast, only small amounts of gastric contents were delivered into the duodenum. This transfer occurred during periods of irregular motor activity recorded along the gastroduodenal junction, which occupied less than 25% of the recording time. The patterns of flow near the pylorus and beyond the duodenal bulb were correlated to antral and duodenal contractions respectively. 4. After a meal, gastric emptying occurred intermittently and was related to enhanced antral motor activity beyond the duodenal bulb; digesta flowed in clusters of gushes which were related to the duodenal contractions. 5. It is concluded that the mechanical role of the duodenal bulb is to change the intermittent juxtapyloric flow of digesta into a uniform flow at the duodenal level.
Properties of calcium stores and transient outward currents in single smooth muscle cells of rabbit intestine.
Authors: Bolton T B , Lim S P
Published: December 2014

1. Single dispersed cells obtained by collagenase treatment of longitudinal muscle of rabbit small intestine were voltage clamped with low‐resistance patch pipettes and membrane current was measured. 2. In cells held at ‐20 or ‐30 mV, a discharge of spontaneous transient outward currents (STOCs) was usually seen; these are believed to represent the sporadic release of calcium from storage sites in the cell in relation to TEA‐sensitive, 4 AP‐resistant, calcium‐activated potassium channels. 3. Caffeine (20 mM) externally applied, accelerated and then abolished STOCs; carbachol (0.1 mM) had similar effects; the initial burst of STOCs was often carried on a large, temporary, outward current which could occur alone. This was suggested to be caused by the rapid release of stored calcium in relation to calcium‐activated potassium channels. 4. If STOCs were abolished by caffeine (or carbachol) then carbachol (or caffeine) did not evoke outward current indicating that these drugs act on the same calcium store but by different pathways. Inclusion of ryanodine (10(‐8)‐10(‐4) M) in the patch pipette abolished STOCs soon after establishing whole‐cell recording mode; afterwards, outward current to caffeine or to carbachol could not be evoked. 5. STOCs were quickly abolished in cells patched with pipettes filled with GTP gamma S (0.1‐1 mM) or Gpp(NH)p (0.1‐1 mM) but were large or normal in size in cells where GDP beta S (0.1‐1 mM) was included in the pipette. GTP gamma S or Gpp(NH)p in the cell abolished outward current to caffeine or to carbachol, but had no effect on calcium‐activated potassium channel activity in isolated patches or on a TEA‐sensitive, 4‐AP‐resistant, outward potassium current evoked in single cells by stepping positively from a ‐20 mV holding potential. These results suggest that the effect of guanine nucleotide analogues are on the calcium store rather than on calcium‐activated potassium channels. 6. The effects of GTP gamma S or Gpp(NH)p could be explained if they depleted calcium stores via a G‐protein mechanism; this effect may involve activation of phospholipase C enzyme (PLC) and D‐myo‐inositol 1,4,5‐trisphosphate (IP3) production as well as a direct effect on stores. However a separate G‐protein‐independent pathway of activation of PLC by muscarinic receptor activation may exist as calcium release by carbachol was large or normal in cells filled with GDP beta S.
Anomalous voltage dependence of channel blockade at a crustacean glutamate‐mediated synapse.
Authors: Lingle C J
Published: December 2014

1. The voltage dependence and concentration dependence of blockade of glutamate‐activated currents by the diquaternary amine, chlorisondamine, were examined in a marine crustacean muscle. 2. Chlorisondamine results in the splitting of focally recorded synaptic current decays into two exponential components. The fast component becomes faster with increases in drug concentration and with hyperpolarization. The slow decay rate is unchanged or faster with hyperpolarization and the relative amplitude of the slow component is increased with hyperpolarization. 3. The alteration of synaptic current decay rates by chlorisondamine over the range of 5 to 100 microM and ‐80 to ‐140 mV is quantitatively consistent with a simple channel blockade model with a zero‐voltage blocking rate of 6 x 10(5) M‐1 s‐1 at 12 degrees C with a voltage dependence of about 40 mV per e‐fold change. The unblocking rate is about 5 s‐1 at 0 mV and increases with hyperpolarization with a voltage dependence of about 30 mV per e‐fold change. 4. The dose dependence and voltage dependence of blockade of ionophoretically activated glutamate currents by chlorisondamine are qualitatively consistent with the kinetic estimates. 5. The anomalous voltage dependence of the unblocking process is considered in terms of the possibility that the relief from blockade by chlorisondamine occurs by transit of chlorisondamine through the ion channel opened by glutamate.
Head‐free pursuit in the human of a visual target moving in a pseudo‐random manner.
Authors: Barnes G R , Lawson J F
Published: December 2014

1. Head and eye movements have been recorded in man during head‐free pursuit of a target moving in a pseudo‐random manner in the horizontal plane with a motion stimulus composed of the sum of four sinusoids. 2. In an initial experiment the three lowest frequencies remained constant at 0.11, 0.24 and 0.37 Hz, whilst the highest frequency (F4) took values of 0.39, 0.78, 1.56 and 2.08 Hz. Peak velocity of each component was 10 deg/s. When F4 was 0.39 Hz gaze displacement (i.e. the sum of head and eye displacement) was relatively smooth and had a mean velocity gain of 0.95. As F4 was increased gaze displacement contained more saccadic activity and gaze velocity gain for the three lower‐frequency components was significantly (P less than 0.001) reduced to a minimum level of 0.66 when F4 was 1.56 Hz. 3. A similar reduction in gain of the lower‐frequency components was obtained when the velocity of F4 was increased as a ratio of the velocity of the lower frequencies from 0 to 4. 4. When the frequency composition of the stimulus was varied so that the two highest frequencies were closely spaced, gaze velocity gain for the highest frequency was always significantly higher than that of the next lower frequency, indicating a true enhancement of the highest‐frequency component. 5. Changing the lowest‐frequency component of the stimulus resulted in a significant shift in the gaze velocity phase profile as a function of frequency, so that phase advance was always associated with the lowest frequency even when this was as high as 0.89 Hz. 6. These changes in gain and phase of gaze velocity with the frequency content of the stimulus were similar to those previously described for head‐fixed pursuit and visual suppression of the vestibulo‐ocular reflex (VOR) and implicate the frequency‐dependent, non‐linear visual feed‐back mechanisms in gaze control. 7. A number of the non‐linear characteristics of gaze velocity were also observed in a somewhat modified form in the head displacement gains and phases, implying that the drive to the neck muscles is also derived from the same non‐linear visual feed‐back source. 8. The role of the VOR in head‐free pursuit was tested by exposing the subject to whole‐body motion on a turntable which countered the volitional head movement generated by the subject.(ABSTRACT TRUNCATED AT 400 WORDS)
Interactions of cervico‐ocular and vestibulo‐ocular fast‐phase signals in the control of eye position in rabbits.
Authors: Barmack N H , Errico P , Ferraresi A , Pettorossi V E
Published: December 2014

1. Eye movements in unanaesthetized rabbits were studied during horizontal neck‐proprioceptive stimulation (movement of the body with respect to the fixed head), when this stimulation was given alone and when it was given simultaneously with vestibular stimulation (rotation of the head‐body). The effect of neck‐proprioceptive stimulation on modifying the anticompensatory fast‐phase eye movements (AFPs) evoked by vestibular stimulation was studied with a ‘conditioning‐test’ protocol; the ‘conditioning’ stimulus was a neck‐proprioceptive signal evoked by a step‐like change in body position with respect to the head and the ‘test’ stimulus was a vestibular signal evoked by a step rotation of the head‐body. 2. The influence of eye position and direction of slow eye movements on the occurrence of compensatory fast‐phase eye movements (CFPs) evoked by neck‐proprioceptive stimulation was also examined. 3. The anticompensatory fast phase (AFP) evoked by vestibular stimulation was attenuated by a preceding neck‐proprioceptive stimulus which when delivered alone evoked compensatory slow‐phase eye movements (CSP) in the same direction as the CSP evoked by vestibular stimulation. Conversely, the vestibularly evoked AFP was potentiated by a neck‐proprioceptive stimulus which evoked CSPs opposite to that of vestibularly evoked CSPs. 4. Eccentric initial eye positions increased the probability of occurrence of midline‐directed compensatory fast‐phase eye movements (CFPs) evoked by appropriate neck‐proprioceptive stimulation. 5. The gain of the horizontal cervico‐ocular reflex (GHCOR) was measured from the combined changes in eye position resulting from AFPs and CSPs. GHCOR was potentiated during simultaneous vestibular stimulation. This enhancement of GHCOR occurred at neck‐proprioceptive stimulus frequencies which, in the absence of conjoint vestibular stimulation, do not evoke CSPs.
Interactions between hypoxia, acetylcholine and dopamine in the carotid body of rabbit and cat.
Authors: Ponte J , Sadler C L
Published: December 2014

1. Acetylcholine (ACh) and dopamine (DA) were either infused into the carotid artery or applied directly to the surface of the carotid body of twenty‐six rabbits and fifteen cats. Afferent discharge of single chemoreceptor units was recorded at a range of Pa,O2 (arterial O2 pressure) values during drug administration. 2. There were no observable systemic effects of either drug when applied to the surface of the carotid body. 3. Acetylcholine tended to depress afferent discharge when applied to the surface of the rabbit carotid body or when infused into the carotid sinus. In the cat, intracarotid and surface application of ACh had mild and inconsistent effects. DA consistently depressed discharge in both species independent of the route of administration. Antagonists of ACh and DA failed to abolish the chemoreceptor response to hypoxia. 4. The changes in afferent discharge elicited by all drugs were small compared with the range of discharge rates attained with physiological stimuli. The effects of ACh and DA were more marked in hyperoxia than in hypoxia for both routes of administration, disappearing at Pa,O2 values close to 20 Torr (7.5 Torr = 1 kPa). 5. A role for DA in the maintenance of the hypoxic response was investigated in six rabbits. After 15 min of hypoxia (Pa,O2 = 21.8 +/‐ 1.1 Torr; mean +/‐ S.E.M.) the discharge of single chemoreceptor fibres adapted moderately (to 79.3 +/‐ 5.2% of maximum discharge). Following administration of domperidone or haloperidol (1.0‐5.3 mg kg‐1, I.V.) the same fibres responded with equal magnitude to the onset of the hypoxic stimulus but showed a significantly larger adaptation (to 48.5 +/‐ 4.4%). 6. It is concluded that endogenous ACh and DA are unlikely to mediate the transduction process of the carotid body, but DA may play a role in preventing adaptation to a prolonged hypoxic stimulus.
The organization of heterogenic reflexes among muscles crossing the ankle joint in the decerebrate cat.
Authors: Nichols T R
Published: December 2014

1. Mechanical actions of heterogenic (intermuscular) reflexes arising from proprioceptors in flexor and extensor ankle muscles were measured in intercollicular and premammillary decerebrate cats. Length inputs were applied to the freed tendons of one of a pair of muscles crossing the ankle joint and resulting changes in force in both muscles were measured. Interactions between autogenic and heterogenic reflexes were studied by applying length changes to both muscles. 2. A consistent asymmetry was observed in the heterogenic inhibition between the single‐joint antagonists soleus and tibialis anterior (TA). Inhibition from soleus to TA was weak or absent during the reflex activation of TA. In contrast, a strong heterogenic inhibition was consistently observed from TA to soleus during the activation of soleus by a crossed‐extension reflex. The effect of this inhibition in the intact joint is to increase the apparent mechanical stiffness of soleus. 3. Mutual synergism among soleus, medial gastrocnemius (MG) and lateral gastrocnemius (LG) was demonstrated only at low to moderate forces by the observation of excitatory reflexes among them. During a naturally or electrically evoked crossed‐extension reflex, however, a unidirectional inhibitory reflex from MG and LG to soleus was observed. This inhibition increased with force in MG or LG. These results suggest that the knee and ankle joints become more tightly linked mechanically at high forces since the stiffness of the biarticular gastrocnemius muscle predominates over that of the uniarticular soleus. 4. Under quiescent conditions (no resting muscle activation), mutual synergism was obeyed among the ankle extensors soleus, LG and MG and also between the pretibial flexors TA and extensor digitorum longus (EDL). Moreover, inhibition was generally observed between a pretibial flexor and an ankle extensor. Departures from this expected pattern of heterogenic reflexes occurred when the muscle groups were activated by crossed‐extension and flexion reflexes. Reflexes onto soleus, TA and EDL reversed in sign or increased in magnitude. 5. The observed patterns of reflex connectivity among the ankle flexors and extensors were similar in both intercollicular and premammillary preparations, although changes in reflex strength were sometimes noted in cases where a second, lower transection was performed during the experiment. 6. It is argued from the large magnitudes of certain heterogenic reflexes that the mechanical response properties of muscles crossing the ankle joint in the intact animal are not dominated by autogenic reflexes and intrinsic mechanical properties.(ABSTRACT TRUNCATED AT 400 WORDS)
Kinetic properties of the GABAA receptor main conductance state of mouse spinal cord neurones in culture.
Authors: Macdonald R L , Rogers C J , Twyman R E
Published: December 2014

1. The kinetic properties of the main conductance state of gamma‐aminobutyric acidA (GABA) receptor channels from somata of mouse spinal cord neurones in cell culture were investigated using patch clamp techniques. 2. Whole‐cell GABA receptor currents increased in a concentration‐dependent manner from 0.5 to 5 microM. 3. Single‐channel currents were recorded with a main conductance state of 27.2 pS and a less frequent conductance state of 15.9 pS. The main conductance state opened singly and in bursts of several openings. 4. Mean open times of GABA receptor main conductance currents were increased and open‐time frequency histograms were shifted to longer times as GABA concentration was increased from 0.5 to 5 microM. Three exponential functions were required to fit the histograms at all GABA concentrations, suggesting that the channel opened into at least three open states (O1, O2 and O3). The three functions had the same time constants (1.0 +/‐ 0.2, 3.7 +/‐ 0.4 and 11.3 +/‐ 0.5 ms; mean +/‐ S.D.) at each concentration. The increase in long open times with concentration was due to a shift in relative frequency of occurrence of openings from the shortest (O1) to the two longest (O2 and O3) open states. 5. Closed‐time distributions of closures between main conductance state openings were fitted with multiple exponential functions, suggesting that the channel had several closed states. The two shortest time constants (0.24 +/‐ 0.03 and 2.0 +/‐ 0.3 ms) were concentration independent (0.5 to 5 microM). Three longer time constants decreased as concentration increased. 6. Bursts were defined as groups of openings surrounded by closures greater than a critical closed time (tc = 5 ms). Mean burst durations were increased and burst duration frequency histograms were shifted to longer times as GABA concentration was increased from 0.5 to 5 microM. Burst‐duration frequency histograms were best fitted with three exponential functions. The time constants were concentration independent and were 1.0 +/‐ 0.2, 5.5 +/‐ 0.2 and 29.8 +/‐ 1.6 ms. The increase in burst duration with concentration was due to a relative shift from short duration bursts to longer duration bursts. 7. The shortest burst time constant was similar to the shortest open time constant suggesting that there was a population of single openings of short duration. The two longest burst time constants were longer than the two longest open time constants, suggesting that the bursts from the two longest burst components were composed of two or more openings.(ABSTRACT TRUNCATED AT 400 WORDS)