bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in electrical properties and quantal current during growth of identified muscle fibres in the crayfish.
Authors: Lnenicka G A , Mellon D
Published: December 2014

The muscle fibre electrical properties, miniature excitatory junctional current (m.e.j.c.) and miniature excitatory junctional potential (m.e.j.p.) were studied during growth of an identified crayfish muscle fibre from a diameter of 20 to 400 microns. The specific membrane resistance (Rm), and the specific internal resistance (Ri), of the muscle fibre were independent of fibre diameter (d) during growth. The current‐voltage relation has a similar shape in large and small fibres, indicating that voltage dependence of Rm does not change during growth. The input resistance (R0) was approximately proportional to d‐1.5, as predicted theoretically. The specific membrane capacitance (Cm) and the membrane time constant (Tm) increased linearly with fibre diameter, apparently as a result of the contribution of the tubular capacitance to Cm. The decrease in R0 and the increase in Tm should have resulted in a 90‐fold decrease in m.e.j.p. amplitude during growth of the fibre from a diameter of 20 to 240 microns. However, m.e.j.p. amplitude was found to decrease only 21‐fold. This discrepancy was shown to result from an increase in m.e.j.c. amplitude and duration during growth. There was 2.9‐fold increase in m.e.j.c. amplitude and a 2.7‐fold increase in m.e.j.c. duration over the range of muscle fibre growth studied. This increase in the m.e.j.c. apparently results from an increase in the magnitude and duration of the synaptic conductance change produced by a quantum of transmitter. Throughout the range of muscle fibre diameters studied, the muscle fibre effective input impedance for the m.e.j.c. was 17‐19% of R0. This is due to the relatively large Cm and the short duration of the m.e.j.c.
Vestibulo‐ocular reflex, optokinetic response and their interactions in the cerebellectomized cat.
Authors: Godaux E , Vanderkelen B
Published: December 2014

The effects of total ablation of the cerebellum on eye movements were studied in alert adult cats. The normal cat could easily hold a steady eye position after a saccadic movement in the dark. The cerebellectomized animal could not: after a saccade the eye position shifted towards a more central position. Vision reduced this 'post‐saccadic drift'. The sinusoidal vestibulo‐ocular reflex (v.o.r.) was strongly affected by total cerebellectomy. In darkness the v.o.r. gain remained stable at high frequencies (0.5 and 1 Hz) but decreased markedly at lower frequencies to as low as 0.18 at 0.05 Hz. A phase advance (up to 65 degrees at 0.05 Hz) paralleled this gain depression. Velocity characteristics of optokinetic nystagmus (o.k.n.) and optokinetic after‐nystagmus (o.k.a.n.) induced by constant‐velocity full‐field rotation of 60 deg/s amplitude and 60 s duration were studied. The features of o.k.n. (initial velocity, maximal velocity and time constant) were only mildly affected by cerebellectomy. On cessation of visual stimulation when the animal was plunged into darkness, the velocity of the eyes decreased progressively (o.k.a.n.). The time constant of o.k.a.n. was 12.5 s in the normal cat and 4.2 s in the cerebellectomized cat. Furthermore cerebellectomy abolished the secondary o.k.a.n. Optokinetic response was also tested by a set of sinusoidal (0.05‐1 Hz; 3‐20 degrees) full‐field stimuli. The o.k.n. was not abolished but dramatically decreased, especially at higher frequencies. No response could be detected above 0.15 Hz. Visual suppression of inappropriate vestibulo‐ocular reflex was still possible but was mildly impaired after cerebellectomy. Visual suppression could only be detected with stimuli below 0.25 Hz. Visual suppression of caloric nystagmus was studied in the normal cat. A clear dependence of the effectiveness of visual suppression on the velocity of the nystagmus was demonstrated. In the cerebellectomized cat, the visual suppression of caloric nystagmus was lost when tested on nystagmus velocities above 20 deg/s but remained when tested on nystagmus velocities below 20 deg/s. The relationship between cerebellectomy and the loss of visual suppression of caloric nystagmus was found to be at least partially indirect: cerebellectomy increased the velocity of caloric nystagmus, and visual suppression was usually less effective at higher velocities.
Firing properties of single human motor units during locomotion.
Authors: Grimby L
Published: December 2014

The discharge properties of single motor units in the short extensors of the toes were studied during normal locomotion using electromyographic recordings which permitted the identification of single motor unit potentials. The single motor units were recruited in the same order during slowly increasing speed of locomotion as they were during slowly increasing voluntary tension, i.e. motor units with low axonal conduction velocity were recruited before motor units with higher conduction velocity. Low threshold units fired five to ten times at 80‐40 ms intervals in each step cycle during walking at normal speed. Motor units with moderately high thresholds fired once or only a small number of times in each cycle at shorter interspike intervals. High threshold motor units did not participate in the step cycle during walking at normal speeds but fired in short high‐frequency bursts in corrective movements.
On the two subdivisions and intrinsic synaptic connexions in the submandibular ganglion of the rat.
Authors: Kawa K , Roper S
Published: December 2014

Parasympathetic neurones in the submandibular ganglion of the rat innervate the submandibular and sublingual salivary glands. Neurones which innervate the submandibular gland (s.m. neurones) are usually located along the salivary ducts which drain both glands. Neurones which innervate the sublingual gland (s.l. neurones) are located in the thin sheet of tissue which lies between the salivary ducts and the lingual nerve. The existence and characteristics of intrinsic synaptic connexions were studied electrophysiologically in these two divisions of the submandibular ganglion. Three days or more after denervating the ganglion two types of excitatory intrinsic synaptic potentials‐‐chemical and electrical‐‐were recorded in ganglion cells. Chemical synaptic responses were reversibly blocked by nicotinic antagonists such as hexamethonium (10 microM) and D‐tubocurarine (100 microM). Intrinsic chemical synapses were common among s.m. neurones (present in 72% of neurones) but only 12% of s.l. neurones were coupled with chemical synapses. Electrical coupling was found among 31% of s.m. neurones but was not observed between s.l. neurones. Electrotonic coupling in s.m. neurones in denervated and intact ganglia was directly demonstrated by impaling adjacent neurones with separate micro‐electrodes. The average coupling ratio for current pulses injected into one cell and recorded in the adjacent cell was 0.06. During the first 30 days after birth, the number of synaptic inputs from preganglionic (chorda tympani) axons was markedly reduced in both s.m. and s.l. neurones, whereas the incidence of electrical synaptic connexions remained unchanged. The effect of long‐term denervation (up to 4 months) on intrinsic synapses was examined. The membrane properties of the parasympathetic neurones and the intrinsic synaptic connexions were maintained without marked changes. It is concluded that the submandibular ganglion in the rat consists of two distinct populations of parasympathetic neurones. The two classes of neurones differ in (1) their location within the ganglion, (2) their target organs and (3) the incidence of intrinsic synapses. Possible mechanisms for the development, maintenance and function of these intrinsic synapses are discussed.
The development of stability of respiration in human infants: changes in ventilatory responses to spontaneous sighs.
Authors: Fleming P J , Goncalves A L , Levine M R , Woollard S
Published: December 2014

Serial respiratory recordings using impedance pneumography and barometric plethysmography were made from shortly after birth to 7 months in fifteen normal full‐term infants. Each recording was made with the infant asleep and sleep state was estimated from records of electroencephalogram and electro‐oculogram made in parallel. The respiratory records obtained during non‐rapid eye movement (r.e.m.) sleep were analysed with computer assistance and stretches of the record, approximately 1 min before and up to 2 min after a spontaneous sigh and ensuing apnoeic pause, were processed and presented as sequential values of the fractional deviation of VE, the breath by breath minute volume, from the mean. That part of the sequence which represented the respiratory response to the sigh was then fitted with second order equations representing the critically or underdamped response. The results were presented for each curve in terms of xi, the damping ratio and omega n, the frequency of the undamped respiratory oscillation. Three‐quarters of the responses could be so fitted with an error of 20% or less. The residual responses were mainly from infants within a few days of birth. In the youngest infants (4 days or less), the respiratory response to a sigh was highly stable but sluggish: during the period 4‐8 days to 3‐4 months, the oscillatory period diminished from ca. 25‐12 s and respiration was potentially unstable since a small reduction in the damping factor would cause prolonged oscillation while, from 3‐4 months, the more mature type of response which was stable with a rapid recovery supervened. The possible mechanisms responsible for this trend are discussed in terms of the factors thought to determine respiratory stability in the adult together with the possible relevance of the results to the normal process of respiratory adaptation at birth and to the respiratory difficulties encountered by some infants in the new‐born period and early infancy.
Functional, structural and chemical correlates of sprouting of intact preganglionic sympathetic axons in the guinea‐pig.
Authors: Fonnum F , Maehlen J , Njå A
Published: December 2014

Intact preganglionic axons can sprout and form new functional synaptic connexions with neurones in the partially denervated superior cervical ganglion of the guinea‐pig (Maehlen & Njå, 1981). In the present work we have examined to what extent the degree of sprouting, as measured by intracellular recording, is paralleled by changes in ultrastructural and neurochemical parameters. The mean number of preganglionic axons innervating each neurone, as estimated by intracellular recording from ganglion cells during stimulation of the individual ventral roots, was reduced from about eleven to about two immediately after the partial denervation. However, 5‐7 weeks after the operation, when sprouting was complete, each neurone was innervated on average by about seven axons. The estimated mean amplitude of the synaptic potential elicited by each innervating axon (about 5 mV) was only slightly increased after sprouting. Counts of the number of synaptic profiles per unit area of electron microscopical sections of the ganglion were reduced to about 15% of normal 3‐4 days after the operation, and increased to about 60% of normal after sprouting (5‐7 weeks). The activity of the enzyme choline acetyltransferase was about 20% of the normal value in ganglia examined 3‐4 days after partial denervation. After sprouting (5‐7 weeks), this value was increased to about 35% of that in normal ganglia. These results show that intact preganglionic sympathetic axons have a substantial growth potential. However, the increase in the choline acetyltransferase activity was smaller than the increase in electrophysiological and ultrastructural measurements. Therefore, compensatory axonal branching and synapse formation may cause a reduction in the supply of choline acetyltransferase to each presynaptic terminal from the parent soma.
Electrophysiological properties of guinea‐pig thalamic neurones: an in vitro study.
Authors: Jahnsen H , Llinás R
Published: December 2014

The electroresponsive properties of guinea‐pig thalamic neurones were studied using an in vitro slice preparation. A total of 650 cells were recorded intracellularly comprising all regions of the thalamus; of these 229 fulfilled our criterion for recording stability and were used as the data base for this report. The resting membrane potential for thirty‐four representative neurones which were analysed in detail was ‐64 +/‐ 5 mV (mean +/‐ S.D.), input resistance 42 +/‐ 18 M omega, and action potential amplitude 80 +/‐ 7 mV. Intracellular staining with horseradish peroxidase and Lucifer Yellow revealed that the recorded cells had different morphology. In some their axonal trajectory characterized them as thalamo‐cortical relay cells. Two main types of neuronal firing were observed. From a membrane potential negative to ‐60 mV, anti‐ or orthodromic and direct activation generated a single burst of spikes, consisting of a low‐threshold spike (l.t.s.) of low amplitude and a set of fast superimposed spikes. Tonic repetitive firing was observed if the neurones were activated from a more positive membrane potential; this was a constant finding in all but two of the cells which fulfilled the stability criteria. The l.t.s. response was totally inactivated at membrane potentials positive to ‐55 mV. As the membrane was hyperpolarized from this level the amplitude of the l.t.s. increased and became fully developed at potentials negative to ‐70 mV. This increase is due to a de‐inactivation of the ionic conductance generating this response. After activation the l.t.s. showed refractoriness for approximately 170 ms. Deinactivation of l.t.s. is a voltage‐ and time‐dependent process; full de‐inactivation after a step hyperpolarization to maximal l.t.s. amplitude (‐75 to ‐80 mV) requires 150‐180 ms. Membrane depolarization positive to ‐55 mV generated sudden sustained depolarizing 'plateau potentials', capable of supporting repetitive firing (each action potential being followed by a marked after‐hyperpolarization, a.h.p.). The a.h.p. and the plateau potential controlled the voltage trajectory during the interspike interval and, with the fast spike, constitute a functional state where the thalamic neurone displayed oscillatory properties. Frequency‐current (f‐I) plots from different initial levels of membrane potential were obtained by the application of square current pulses of long duration (2s). From resting membrane potential and from hyperpolarized levels a rather stereotyped onset firing rate was observed due to the presence of the l.t.s.(ABSTRACT TRUNCATED AT 400 WORDS)
A patch‐clamp study of the partial agonist actions of tubocurarine on rat myotubes.
Authors: Takeda K , Trautmann A
Published: December 2014

Single channels activated by (+)‐tubocurarine (curare) were recorded from rat myotubes using the patch‐clamp technique. The agonist‐like action of curare does not result from a contaminant molecule, as the same effects were observed with curare purified by high‐performance liquid chromatography. A curare‐activated channel can adopt two levels of conductance: full (F) or partial (P). The F state has a slope conductance of 40 pS (identical to that of the acetylcholine (ACh)‐activated channel) and the P state has a conductance of 13 pS. At low concentrations of agonist (ACh or curare), the distribution of channel open times is biphasic. The briefer channels may result from the binding of a single agonist molecule whereas the longer‐lived channels probably occur following the binding of two agonist molecules. The mean open time of the F state decreases with increasing curare concentration. It is shown that band‐width limitations are likely to account for only a very small part of this observed reduction. In contrast, the mean open time of the P state is independent of the concentration of curare. A simple interpretation is that the F state is susceptible to channel blockade by curare, whereas the P state is not. The P state preceded the F state almost as often as it followed the F state; it can also be observed separately from the F state. The fraction of events including a P state increases from about 4% in the presence of 1 microM‐curare to 30% at 100 microM‐curare. This fraction is also increased by hyperpolarization. When the curare concentration is increased, the F‐state frequency first increases and then decreases at higher concentration. This frequency is also decreased by hyperpolarization. The decrease in F‐state frequency is probably related to channel blockade by curare; it cannot be wholly accounted for by problems associated with limited time resolution. A synthetic analogue of curare, (+)‐ tubocurine dimethiodide presents an agonist activity similar to that of curare but with a faster closing rate for both F and P states. The various actions of curare are summarized in two possible models where the P state is interpreted as either a partially open channel or a channel which is partially blocked.
Interaction of cholecystokinin and vasoactive intestinal polypeptide on function of mouse pancreatic acini in vitro.
Authors: Burnham D B , McChesney D J , Thurston K C , Williams J A
Published: December 2014

In isolated mouse pancreatic acini, vasoactive intestinal polypeptide (VIP) and secretin potentiated amylase release stimulated by cholecystokinin (CCK). VIP (1‐100 nM) or secretin (100‐1000 nM) alone elicited a negligible secretory response, whereas in combination with CCK, these agents induced a significantly larger response. VIP increased maximal amylase release elicited by CCK without affecting the potency with which CCK stimulated secretion. The phosphodiesterase inhibitor, 3‐isobutyl‐1‐methyl xanthine (IBMX), from 0.03‐1.0 mM had effects on secretion similar to those of VIP. VIP, IBMX and 8‐Br‐cyclic AMP, all of which act through or mimic the action of cyclic AMP, potentiated the secretory response to maximal concentrations of CCK, carbamylcholine and the ionophore A23187, all of which act via intracellular calcium. In contrast to amylase release, stimulation of acinar glucose transport by CCK or carbamylcholine was not augmented by VIP, secretin, IBMX or 8‐Br‐cyclic AMP. The results indicate that for amylase release from mouse pancreas, secretagogues acting via cyclic AMP potentiate those acting via calcium. However, potentiation does not apply to all biological responses of the pancreatic acinus and each response must be studied individually.
Reciprocal inhibition between the muscles of the human forearm.
Authors: Day B L , Marsden C D , Obeso J A , Rothwell J C
Published: December 2014

Peripheral and central mechanisms of reciprocal inhibition between antagonist muscles in the forearm have been studied in ten human subjects. H reflexes were evoked in flexor muscles by stimulating the median nerve with single shocks at around motor threshold intensity. Peripheral inhibition of the flexor H reflex was produced by motor threshold stimulation with a single shock of the radial nerve supplying the extensor muscles. The conditioning radial nerve stimulus produced inhibition of the flexor H reflex consisting of three phases. In some individuals, an H reflex could be evoked in extensor muscles of the forearm. Stimulation of the median nerve produced inhibition of the extensor H reflex with a similar time course to that from extensors to flexors. The first phase of inhibition was apparent when the test median nerve shock was given from 1 ms before to 3 ms after the conditioning radial nerve shock. It was abrupt in onset and short in duration and could be evoked with a conditioning stimulus intensity as low as 0.75 X motor threshold. The second and third phases of inhibition were evident when the conditioning radial nerve stimulus preceded the median nerve test shock by 5 to 50, and 50 to 500 ms respectively. The characteristics of these later phases of inhibition are to be the subject of a separate report. The difference in timing of the peak initial short‐latency inhibition from extensor to flexor and from flexor to extensor muscles enabled an estimate to be made of the central synaptic delay of the inhibitory process. This method yielded a central delay of 0.95 ms in excess of that of the H reflex. We conclude that the first phase of inhibition is mediated via large group I afferents acting through a single inhibitory interneurone . Central inhibition of the flexor H reflex was demonstrated with the radial nerve anaesthetized by injection of local anaesthetic at the elbow. Subjects were asked to try to contract the paralysed extensor muscles. Under this condition, attempted voluntary wrist extension inhibited the flexor H reflex even though no movement occurred. A shock was delivered to the radial nerve at a site proximal to the anaesthetic block. When the shock was applied in conjunction with an attempted voluntary contraction of the paralysed extensor muscles, the depth of inhibition was greater than that predicted from the effect of either a shock or a willed contraction acting independently.(ABSTRACT TRUNCATED AT 400 WORDS)
Changes in vergence mediated by saccades.
Authors: Enright J T
Published: December 2014

When binocular fixation is shifted between two targets which require change in vergence as well as an equivalent or greater alteration in the mean visual direction, the observed eye motions do not‐‐as asserted by Yarbus (1957) and widely accepted today‐‐consist of slow symmetrical change in vergence, upon which a conjugate (binocularly balanced) saccade is additively superimposed. In all tested target configurations, an unexpectedly large fraction of the total change in vergence occurred during the saccades; observed values ranged from about 40% in certain tasks, to essentially 100% when large version (4 degrees) was combined with small vergence change (less than 1 degree). In these latter situations, binocular congruence can be restored within about 50 ms by appropriately unbalanced saccades, rather than about 500 ms, as expected if slow fusional vergence movement were required. When larger vergence changes are demanded, additivity between vergence movement and conjugate saccade is also violated in that the rate of vergence change during the saccades is several‐fold larger than the rate before the saccade or during subsequent completion of the required change in vergence. Furthermore, the residual fusional vergence movement observed in these tests was usually strongly asymmetrical, and often almost entirely monocular. Vertical saccades are nearly as effective as horizontal saccades in mediating a large fraction of an intended change in vergence. In saccades, which contributed strongly to (or fully mediated) an intended vergence change, target‐specific binocular differences in saccadic excursion of as much as 40‐50% were observed; hence, these eye movements are not fully yoked, as the term 'conjugate' implies. Instead, the eyes behave in such situations as though visual information from each eye is processed separately prior to the saccade, in order to generate the neural signals which control open‐loop saccadic movement of the eye.
The dependence of force and shortening velocity on substrate concentration in skinned muscle fibres from Rana temporaria.
Authors: Ferenczi M A , Goldman Y E , Simmons R M
Published: December 2014

The force‐velocity relation was determined in fully activated skinned fibres from frog muscle at concentrations of the substrate, magnesium adenosine triphosphate (MgATP), ranging from 10 microM to 10 mM. The ionic strength of the solutions was 200 mM, temperature 0‐5 degrees C, pH 7.1. The activation procedure of Moisescu (1976) was used to raise the calcium concentration rapidly in the interior of the fibres. A re‐phosphorylating system (creatine kinase and creatine phosphate) was used to maintain the MgATP concentration in the fibres. Isotonic releases were performed using a fast servo‐controlled motor and tension transducer. Releases to a pre‐determined tension level relative to the isometric tension were made using a novel normalizing circuit. In some of the experiments changes of sarcomere length were recorded using the diffraction device described in the preceding paper (Goldman & Simmons, 1984). There was satisfactory agreement between velocities determined from the total length change and the sarcomere length change. The isometric tension showed a biphasic dependence on MgATP concentration. Tension increased with MgATP concentration from 1 microM to reach a peak at about 30‐100 microM and decreased by about 20% from the value at the peak with further increase in the MgATP concentration to 5 mM (about the physiological concentration). At 5 mM‐MgATP, the isometric tension was approximately the same as in intact fibres, if allowance is made for the increase in cross‐sectional area that occurs when the surface membrane is removed. The maximum velocity of shortening, Vmax, was obtained by fitting the force‐velocity relation using Hill's (1938) equation. Vmax showed a roughly hyperbolic dependence on MgATP concentration, with a Km of 0.47 mM. At 5 mM‐MgATP, the value of Vmax was 2.16 muscle lengths per second, which is similar to that of intact fibres. a/P0, the parameter of Hill's (1938) equation that is related to the curvature of the force‐velocity relation, showed a slight decrease with increasing MgATP concentration. Its value at 5 mM‐MgATP of 0.16 is somewhat lower than found for intact fibres. The results are discussed in terms of a simple model based on the biochemical cycle of hydrolysis of ATP by actomyosin in solution. The decrease of tension from about 30 microM to higher concentrations of MgATP can be related to the dissociating effect of MgATP on actomyosin. The increase of isometric tension from 1 to 30 microM‐MgATP is discussed in terms of two types of rigor attachment of cross‐bridges which support different amounts of tension.(ABSTRACT TRUNCATED AT 400 WORDS)
Isolated perfused rabbit coronary artery and aortic strip preparations: the role of endothelium‐derived relaxant factor.
Authors: Griffith T M , Henderson A H , Edwards D H , Lewis M J
Published: December 2014

Isolated perfused coronary arteries and aortic ring preparations of rabbits were studied, both with intact endothelium and with endothelium removed by K‐rich solution and friction respectively. Constrictor dose‐responses to histamine, acetylcholine, phenylephrine and 5‐hydroxytryptamine (5‐HT) were measured. They were greatly depressed by the presence of endothelium in coronary preparations. In aortic preparations endothelium affected dose‐responses relatively little, depressing the response to acetylcholine but apparently increasing the responses to the other three agents. Acetylcholine relaxed pre‐constricted coronary or aortic preparations but only when endothelium was present. This relaxation was inhibited by quinacrine or hydroquinone. Aortic preparations had resting tone which could be increased by hydroquinone if endothelium was present, suggesting continual release of endothelium‐derived relaxant factor (EDRF) at rest. When allowance was made for basal EDRF activity in aortic preparations, the maximal constrictor response to acetylcholine remained lower in the presence of endothelium, consistent with acetylcholine stimulation of EDRF, but maximal constrictor responses to the other three agents were the same with and without endothelium, suggesting that the direct constrictor response overrides EDRF activity.
Rapidly activating hydrogen ion currents in perfused neurones of the snail, Lymnaea stagnalis.
Authors: Byerly L , Meech R , Moody W
Published: December 2014

Cells from the circumoesophageal nerve ring of the pond snail Lymnaea stagnalis were internally perfused with solutions containing Cs aspartate, EGTA and pH buffers. Time‐dependent, voltage‐dependent 'residual' outward currents were observed at positive potentials. They were found to be carried largely by H+. The outward H+ currents were reduced by high internal pH, low external pH, external Cd2+ and 4‐aminopyridine. External tetraethylammonium ions reduced the H+ currents but had a more effective blocking action on the K+ currents in these cells. All five agents reduced the maximum H+ conductance. In addition Cd2+, low external pH and high internal pH were found to shift the voltage dependence of the H+ current to more positive potentials. There was no significant difference between H+ currents recorded with the internal pCa2+ about 7 and those recorded with the internal pCa2+ near 5. It is likely that the H+ channel described here provides the basis for the increase in H+ permeability described by Thomas & Meech (1982) in depolarized Helix neurones. As judged by their sensitivity to different antagonists, H+ channels are unlike any other previously described channel. They are highly selective for protons and we suggest that their role in molluscan neurones is to compensate for the rapid intracellular acidification which is generated by trains of action potentials (Ahmed & Connor, 1980).
Contribution of cerebellar intracortical inhibition to Purkinje cell response during vestibulo‐ocular reflex of alert rabbits.
Authors: Miyashita Y , Nagao S
Published: December 2014

Ionophoretic application of bicuculline, an antagonist of gamma‐aminobutyric acid (GABA), was used to examine the contribution of intracortical inhibition to vestibular responses of Purkinje cells in the cerebellar flocculus of alert rabbits. Purkinje cells were sampled extracellularly (with triple‐barrelled micropipettes) from the floccular area where electrical stimulation through the micro‐electrode evoked abduction of the ipsilateral eye, indicating its close functional relationship to the horizontal vestibulo‐ocular reflex. These cells exhibited frequency modulation of simple spike discharges in‐phase or out‐phase with sinusoidal head rotation (0.5 cycles/s, 5 degrees peak‐to‐peak) in the horizontal plane. Bicuculline was ejected ionophoretically through one barrel with a 20‐60 nA current. The pharmacological effectiveness of the ejected bicuculline was confirmed for each Purkinje cell by its blocking action upon the depressant action of GABA applied ionophoretically through another barrel. Bicuculline usually shifted the simple spike modulation in the in‐phase direction: it reduced the amplitude of out‐phase modulation in three cells, converted out‐phase modulation to the in‐phase type in four cells, and increased in‐phase modulation in five cells. In three other cells, however, bicuculline shifted the modulation in the out‐phase direction. Because bicuculline application usually increased the resting discharge level of a Purkinje cell, ionophoretic application of DL‐homocysteate was used in ten Purkinje cells to control for the effect of a generalized increase in excitability. In contrast to bicuculline, DL‐homocysteate generally induced a slight increase of the simple spike modulation regardless of the phase relationship. Since frequency modulation of the simple spike discharges of flocculus Purkinje cells is presumed to contribute to the control of vestibulo‐ocular reflexes, these results point to an important functional role of intracortical post‐synaptic inhibition in the cerebellar cortex.
The influence of variations in muscle fibre composition on muscle strength and cross‐sectional area in untrained males.
Authors: Maughan R J , Nimmo M A
Published: December 2014

The force produced by a maximum voluntary isometric contraction of the knee‐extensor muscles was measured in a group of fifteen healthy young male volunteers. All subjects were untrained at the time of the study. The cross‐sectional area of the knee‐extensor muscles was measured at the mid‐thigh level using computed tomography. Skeletal muscle samples were obtained by needle biopsy from the mid‐point of m. vastus lateralis of the stronger leg of each subject. Samples were mounted, frozen and sectioned for histochemical analysis. On the basis of the pH dependent lability of the myosin ATP‐ase reaction, fibres were classified as Type I, Type IIA or Type II B. Using computerized planimetry, muscle fibre cross‐sectional areas were measured on serial sections stained for succinate dehydrogenase activity. As previously described, muscle strength (maximum voluntary contraction) was correlated with the muscle cross‐sectional area (r = 0.70, P less than 0.01). The ratio of strength (in N) to cross‐sectional area (in cm2) was 8.92 +/‐ 1.01 (mean +/‐ S.D.) with a wide range of values, from 7.09 to 10.85. Muscle fibre composition of m. vastus lateralis in these subjects was 46.1 +/‐ 10.5% Type I, 42.8 +/‐ 11.4% Type IIA and 11.1 +/‐ 9.7% Type IIB. After correction for differences in the cross‐sectional areas of the different fibre types, the proportions of total area occupied by the different fibre types were: 43.6 +/‐ 11.9% Type I, 46.4 +/‐ 13.1% Type IIA and 10.0 +/‐ 9.1% Type IIB. No relationship was observed to exist between muscle strength and muscle fibre composition. Similarly, the muscle strength/cross‐sectional area ratio was not related to the proportions of the different fibre types present or to the fraction of the total cross‐sectional area occupied by the different fibre types. From the results it can be concluded that there is no difference in the force per unit area which can be generated by the different muscle fibre types present in human skeletal muscle. Variations in muscle fibre composition between individuals cannot, therefore, account for the large variations observed in the ratio of strength to muscle cross‐sectional area.
A mutation that alters properties of the calcium channel in Paramecium tetraurelia.
Authors: Hinrichsen R D , Saimi Y
Published: December 2014

The membrane properties of a new mutant of Paramecium tetraurelia, dancer, were compared under voltage clamp with those of the wild type. The Ca2+ current was isolated and examined using CsCl‐filled electrodes and tetraethylammonium in the bath solution to block K+ channels. The amplitude of the Ca2+ transient was not altered by the mutation. However, the Ca2+ current in the mutant inactivated more slowly and less extensively: hence a larger sustained Ca2+ current remained in the mutant. A change in the time course of the deactivation of the Ba2+ current was observed in the mutant. This mutational change is not likely to be the consequence of the Ca2+‐channel inactivation because it is seen in the Ba2+ solution where there is little inactivation of the current. Other measured properties of the Ca2+ channel, the voltage‐dependent K+ current, and the resting properties of the membrane were normal in the mutant. The Ca2+‐activated K+ current and the Ca2+‐activated Na+ current were larger in the mutant than in the wild type, consistent with a greater elevation of free intracellular Ca2+ during depolarization in the mutant. It is likely that the mutation causes an alteration in the Ca2+‐channel structure or in its immediate environment and thereby affects the inactivation and deactivation processes of the Ca2+ channel. As would be expected from the greater Ca2+ current, the mutant tends to generate all‐or‐none Ca action potentials as opposed to the graded action potentials in the wild type.
Extracellular ions and excitation‐contraction coupling in frog twitch muscle fibres.
Authors: Miledi R , Parker I , Zhu P H
Published: December 2014

Intracellular calcium transients were recorded from voltage‐clamped frog twitch muscle fibres using Arsenazo III. The possible role of extracellular ions in excitation‐contraction (e.‐c.) coupling was examined using ion substitutions and blocking drugs in the bathing medium. Parameters measured included the Arsenazo response size to a standard depolarizing pulse (5 ms, 0 mV) and the strength‐duration curve for threshold Arsenazo signal. Addition of tetrodotoxin (TTX) decreased the response size to small (‐30 mV, 5 ms), but not large (+30 mV, 10 ms) depolarizations, probably because of poor voltage clamp of the tubular membrane in the absence of TTX. Clamping TTX‐treated fibres with the wave form of a recorded action potential gave an Arsenazo response similar to that elicited by the normal action potential (at 10 degrees C). Complete substitution of sodium (by choline, lithium or Tris) or chloride (by methyl sulphate or maleate) in the bathing solution gave no appreciable changes in the size of the Arsenazo response. Reduction of extracellular free [Ca2+] to low levels using EGTA caused a slight reduction in the calcium signal elicited by the standard depolarization (to 74% after a few hours, and to 62% after 2 days; temperature 5‐10 degrees C). The strength‐duration curve was unchanged. Arsenazo responses about 75% of the control size could be elicited in high potassium solution (42 mM‐K2SO4) by strong (+80 mV, 20 ms) depolarizations, after re‐polarizing the fibres to ‐90 mV for a few minutes. The voltage dependence of activation was shifted to more positive potentials in this solution. Tetraethylammonium (TEA) bromide at a concentration of 20 mM did not alter the Arsenazo signal, whilst 120 mM‐TEA reduced the response by 25%. 3,4‐diaminopyridine (DAP) reduced the size of the Arsenazo signal at a concentration of 5 mM, and caused spontaneous release of calcium from the sarcoplasmic reticulum (s.r.) in the absence of membrane potential changes. The Arsenazo signal elicited by an action potential was enhanced by 1 mM‐DAP, because of prolongation of the action potential, but was depressed by higher concentrations. We conclude that e.‐c. coupling does not involve the influx of any external ions into the muscle fibre. If a current flow between the T‐tubules and the s.r. is involved in e.‐c. coupling, then this is probably carried by an efflux of potassium ions.
Simultaneously active and inactive synapses of single Ia fibres on cat spinal motoneurones.
Authors: Henneman E , Lüscher H R , Mathis J
Published: December 2014

A technique is described for recording large numbers of individual or single‐fibre excitatory post‐synaptic potentials (e.p.s.p.s) from single motoneurones by means of spike‐triggered averaging. The cable properties of the motoneurones were calculated from the decay time course of a voltage transient in the motoneurone following a current pulse applied to the soma. From this response a theoretical shape index curve was calculated. Most individual or single‐fibre e.p.s.p.s elicited by impulses in different Ia fibres had simple decay time courses and shape indices that fitted the theoretical shape index curve of the motoneurone from which they were recorded very well. This suggested that the active terminals of these afferent fibres were located within limited post‐synaptic areas. In a few cases the original amplitude, latency and shape of individual e.p.s.p.s changed dramatically when they were re‐averaged 40 min later after the membrane potential had decreased, but was still at an acceptable level. E.p.s.p.s with simple decay time courses changed to e.p.s.p.s with composite decay time courses, presumably due to activation of previously silent synapses. The results suggest that impulses conducted in a single afferent fibre from a muscle spindle do not necessarily activate all of the synapses which the fibre forms on a motoneurone, but may repeatedly fail to activate some endings during prolonged periods of spike‐triggered averaging, while consistently activating others. Evidence regarding the site of transmission failure and the possible mechanism of its relief is discussed.
Serine uptake by luminal and basolateral membrane vesicles from rabbit kidney.
Authors: Kragh-Hansen U , Sheikh M I
Published: December 2014

The mechanism of renal transport of L‐ and D‐serine by membrane vesicles prepared from either whole cortex, pars convoluta or pars recta of rabbit proximal tubule was studied by a rapid filtration technique and by a spectrophotometric method using a potential‐sensitive carbocyanine dye. Transport studies carried out with different salt gradients and by employing various ionophores showed that uptake of both L‐ and D‐serine by luminal membrane vesicles from whole cortex was mediated by an Na+‐dependent and electrogenic transport process. Eadie‐Hofstee analysis of experimental data, obtained under extravesicular greater than intravesicular NaCl gradients, revealed the existence of multiple transport systems for L‐serine but only one system for the D‐isomer. The value of KA (the concentration producing a half‐maximal optical response) for the D‐serine transport system was calculated to be approximately 30 mM. Luminal membrane vesicles from pars convoluta take up both L‐ and D‐serine by a single and common transport system. KA values for L‐ and D‐serine transport were calculated to be 3.7 and 30 mM, respectively. Luminal membrane vesicles from pars recta take up L‐serine by means of two transport systems, one of high affinity (KA = 0.37 mM) and the other of low affinity (KA = 10 mM). By contrast, no D‐serine transport by these membrane vesicles could be detected. Uptake of L‐serine by basolateral membrane vesicles is Na+ independent and electroneutral. Filtration studies showed that the transport is saturable (Km = 25‐30 mM) and is inhibited by the presence of L‐phenylalanine (but not by D‐serine), indicating carrier‐mediated uptake of L‐serine.
Effects of hind limb nerve section on lumbosacral dorsal horn neurones in the cat.
Authors: Brown A G , Fyffe R E , Noble R , Rowe M J
Published: December 2014

The sciatic and saphenous nerves of one hind limb were sectioned in young adult cats anaesthetized with halothane. Between 19 and 55 days later, under chloralose anaesthesia, dorsal horn neurones in the L6 and L7 segments were recorded and their receptive field properties examined. In seven animals recordings were made from identified spinocervical tract, post‐synaptic dorsal column and dorsolateral funicular neurones as well as from neurones that did not project through these pathways. Thirty‐one neurones were intracellularly stained with horseradish peroxidase, and fifty‐three were recorded extracellularly and located by reference to stained cells. In two animals (both 31 days after nerve section) no attempt was made to identify axonal projections of the dorsal horn neurones in order to avoid any effects of cervical cord search stimuli on the cells' properties, but all isolated extracellularly recorded units were examined. On the side ipsilateral to the nerve sections 143 units were recorded. In all experiments, neurones in the medial three‐quarters of the dorsal horn had no discernible cutaneous, mechanosensitive receptive fields between 19 and 55 days after nerve section. There were only two exceptions to this generalization, one neurone being one of the most rostral cells in the sample (in caudal L5) and the other being one of the most caudal cells (in caudal L7). We present evidence to show that neither of these two neurones had inappropriate receptive fields in terms of the somatotopic organization of the dorsal horn. All other neurones with receptive fields on the skin were appropriately located in the somatotopic map laid out in the dorsal horn. There was no evidence for gross anatomical changes in the dendritic trees of dorsal horn neurones following sciatic and saphenous nerve sections. We have been unable to confirm that, following loss of cutaneous receptive fields by peripheral nerve section, dorsal horn neurones in adult cats acquire 'inappropriate' receptive fields. Possible reasons for this are discussed.
The responses of duodenal tension receptors in sheep to pentagastrin, cholecystokinin and some other drugs.
Authors: Cottrell D F , Iggo A
Published: December 2014

The proposal that some post‐prandially released alimentary hormones modify ingestive behaviour and gastric emptying by altering impulse activity in alimentary enteroceptors has been tested using a number of gastrointestinal peptide hormone analogues. These and other drugs were applied to single‐unit afferent preparations of duodenal tension receptors in chloralose‐anaesthetized sheep. In separate experiments the effect of pentagastrin and cholecystokinin on duodenal motor activity was recorded without unitary afferent activity measurements. Local intra‐arterial bolus injections of pentagastrin, cholecystokinin, insulin, prostaglandin, acetylcholine, phenylbiguanide, veratrine, 5‐hydroxytryptamine and bradykinin aroused or enhanced activity in tension receptors. With the exception of a short‐latency effect of insulin B.P., these responses occurred together with local increases in tension and electromyographic activity of the duodenum. Combinations of atropine and hexamethonium reduced duodenal motor activity and abolished most drug‐evoked afferent responses. Intracarotid bolus injections of pentagastrin at first increased, then reduced duodenal tension, electromyographic activity and impulse activity of tension receptors. Cholecystokinin (CCK‐8) injected by this route caused similar alterations of these parameters, and the response was characterized by periods of reduced activity followed by a prolonged excitation of duodenal motility. From the responses to bolus injections of humoral agents it is concluded that some alimentary hormones released after a meal may have a peripheral excitatory action on the tension receptor environment which causes increased afferent activity. The mechanism probably involves both an alteration in duodenal motility and a sensitization of the receptor ending. In addition, the peptide hormones gastrin and cholecystokinin may act centrally to alter duodenal motor control and thus may influence gastric emptying and post‐prandial satiety mechanisms.
The role of spinal cord transmission in the ventilatory response to exercise in man.
Authors: Adams L , Frankel H , Garlick J , Guz A , Murphy K , Semple S J
Published: December 2014

The ventilatory response to electrically induced exercise was studied in thirteen patients with traumatic spinal cord transection at or about the level of T6. The steady‐state and on‐transient responses to this exercise were compared with those obtained in eighteen normal subjects (Adams, Garlick, Guz, Murphy & Semple, 1984). Exercise was produced by surface electrode stimulation of the quadriceps and hamstring muscles so as to produce a pushing movement at 1 HZ against a spring load. At rest there was no significant difference between normals and patients, except that the patients had a lower CO2 elimination (VCO2) and end‐tidal PCO2 (PET,CO2) and a higher heart rate. On exercise the mean rise in VCO2 for the patients was 172 ml min‐1 (S.D. 72), and for the normals was 287 ml min‐1 (S.D. 143). The corresponding mean changes in ventilation (VI) were 4.4 l min‐1 (S.D. 2.2) and 7.6 l min‐1 (S.D. 3.2). However, the ventilatory equivalent for CO2 (delta VI/delta VCO2) in the steady state was not significantly different between patients (26.0, S.D. 5.9) and normals (28.5, S.D. 7.4). In the steady state there was a mean rise in PET,CO2 of 0.9 mmHg (S.D. 1.4) in the normals, and 3.2 mmHg (S.D. 2.7) in the patients, but there was overlap between the two groups. In many experimental runs in both groups, PET,CO2 did not rise, and sometimes fell. Where PCO2 did rise, the ventilatory response to exercise could not be accounted for on the basis of the ventilatory sensitivity to CO2 inhalation. From arterial sampling in three of the patients it was found that when PET,CO2 rose, the corresponding change in Pa,CO2 was less. During the on transient, there was a significant rise in both VCO2 and VI by the second breath in both groups. At the end of the on transient the normal subjects had achieved 84% (S.D. 40) of the steady‐state increase in VCO2 and 88% (S.D. 24) of the increase in VI. The corresponding values for the patients were 67% (S.D. 17) and 77% (S.D. 16) respectively; these differences between normals and patients are significant. The increase of VI during the on transient in the patients was achieved almost entirely by an increase in tidal volume whereas in normals, an increase in respiratory rate was a more important component. We conclude therefore that in man, spinal cord transection with a presumed loss of muscle afferents allows a ventilatory response to electrically induced exercise that cannot be explained by classical chemoreception.(ABSTRACT TRUNCATED AT 400 WORDS)