bluuebunny/crossref_metadata_2025 huggingface dataset:
Submucosal plexus and electrolyte transport across rat colonic mucosa.
Authors: Andres H , Rock R , Bridges R J , Rummel W , Schreiner J
Published: December 2014

Electrolyte transport across two preparations of mucosa from rat colon descendens was compared to determine what influence the submucosal plexus has on electrolyte transport. One preparation consisted of the mucosa, muscularis mucosae, and the submucosal tissue and is referred to as the mucosa‐submucosa preparation. The second preparation obtained by further blunt dissection of the mucosa‐submucosa preparation consisted of only the mucosa and the circular muscle layer of muscularis mucosae and is referred to as the mucosa preparation. Histological studies showed that the submucosal tissue and the longitudinal layer of muscularis mucosae could be removed leaving only the mucosa and the circular layer of muscularis mucosae. The extensive neuronal network of the submucosa was shown when the submucosal tissue and longitudinal muscle layer of muscularis mucosae, which were removed, were stained histochemically for acetylcholinesterase activity. Both the mucosa‐submucosa and mucosa preparations absorbed Na+ and Cl‐ when short‐circuited. However, Na+ and Cl‐ absorption were significantly higher in the mucosa preparation. The increase in Na+ and Cl‐ transport in the mucosa preparation was accompanied with a decrease in the short‐circuit current (Isc), the open‐circuit potential difference (p.d.) and the transmural tissue conductance (Gt) when compared to the mucosa‐submucosa preparation. Tetrodotoxin (TTX), a neurotoxin which blocks specifically the propagation of action potentials in excitable tissues, dose‐dependently decreased Isc and p.d. in the mucosa‐submucosa preparation when added to the serosal solution. The half‐maximal effective concentration of TTX was 5 nM and maximal effective concentration 100 nM. TTX (1 microM) had no effect on Isc or p.d. when added to the mucosal solution. The decrease in Isc and p.d. caused by TTX in the mucosa‐submucosa preparation was accompanied with an increase in Na+ and Cl‐ absorption. TTX caused only a small decrease in Isc and p.d. in the mucosa preparation. However, there was no measurable change in Na+ and Cl‐ transport in the mucosa preparation. The results suggest that spontaneously active neurones from the submucosal plexus have an inhibitory influence on the mucosa. Physical removal of the submucosal plexus or pharmacological blockade of the neurones within the mucosa‐submucosa preparation by TTX led to enhanced absorption, suggesting that the set point of the mucosa for electrolyte transport is at or near a maximal absorptive state. Regulation or modulation of the mucosa may therefore occur by mechanisms that lower this set point, causing an inhibition of absorption of electrolytes.
Synchronous afferent discharge from a passive muscle of the cat: significance for interpreting spike‐triggered averages.
Authors: Hamm T M , Reinking R M , Roscoe D D , Stuart D G
Published: December 2014

Evidence is presented for the existence of synchrony between the spike trains of muscle afferents of the passive cat medial gastrocnemius muscle held at fixed length. Synchrony between the spike trains of a population of muscle afferents was quantified by means of a synchronization index (Is), derived from spike‐triggered averages of the muscle‐nerve neurogram and the rectified neurogram. A previously used test based solely upon the neurogram average (Watt, Stauffer, Taylor, Reinking & Stuart, 1976) is shown to be invalid. The differences between experimentally derived Is values and theoretical Is values derived for the condition of asynchrony were compared to estimated confidence limits for those differences. This comparison revealed that twenty‐two of fifty‐three muscle‐afferent spike trains whose rectified averages satisfied certain conditions for interpreting the Is were synchronized with the discharge of other afferents. The form of the rectified averages of another eight afferents suggested that these afferents might also have been synchronized. Synchrony in the discharge of muscle afferents was found in three experiments in which the neurogram was recorded from a single nerve branch to medial gastrocnemius, as well as in the data of experiments in which the whole muscle nerve was used. The degree of synchrony was similar for Ia, spindle group II and Ib afferents. The magnitude of the synchrony found in these experiments was judged by comparison to the results of analog simulations and the increase in Is values resulting from the application of small, quick stretches to the medial gastrocnemius muscle. The degree of synchrony found on average was approximately equivalent to that of a single spike occurring once for every four discharges of the reference spike train. Simulations were performed to determine the distortion of monosynaptic excitatory post‐synaptic potentials (e.p.s.p.s) obtained by spike‐triggered averaging which would be produced by synchrony between the spike trains of Ia and spindle group II afferents of the magnitude found in this study. These simulations indicate that the apparent amplitude would be increased by approximately 4 microV on average. Both the 10‐90% rise time and the half‐width would increase, the effects being greater for smaller e.p.s.p.s. Consequently, the synchrony found in this study is of most concern in the study of small post‐synaptic potentials, such as those due to spindle group II afferents.
Canine bombesin‐like gastrin releasing peptides stimulate gastrin release and acid secretion in the dog.
Authors: Bunnett N W , Clark B , Debas H T , Del Milton R C , Kovacs T O , Orloff M S , Pappas T N , Reeve J R , Rivier J E , Walsh J H
Published: December 2014

The synthetic mammalian bombesin‐like peptides, canine gastrin releasing peptide 27, 23 and 10, and porcine gastrin releasing peptide 27 were compared with amphibian bombesin 14 and 10 during intravenous infusions into six conscious dogs with chronic gastric cannulae. Gastrin and gastrin releasing peptide were measured in peripherally sampled venous blood by radioimmunoassay and gastric acid secretions were collected. All forms of gastrin releasing peptide stimulated gastrin release and gastric acid secretion in a dose‐dependent manner. The larger canine and porcine peptides were more potent than the decapeptide. Bombesin 14 was more potent than bombesin 10. A rise in the venous concentration of immunoreactive gastrin releasing peptide of only 20 fmol ml‐1 stimulated gastrin release to about 50% of maximal. Gastrin releasing peptide 10 was cleared from the circulation three times faster than the larger forms and this may account for the apparent differences in potency.
Voltage‐dependent potassium currents in developing neurones from quail mesencephalic neural crest.
Authors: Bader C R , Bertrand D , Dupin E
Published: December 2014

Neurones in explants cultured from quail mesencephalic neural crest were studied at different stages of their development using the voltage‐clamp technique. A voltage‐dependent outward current activated by membrane depolarization was identified as a potassium current by the sensitivity of its reversal potential to extracellular potassium. The voltage‐dependent potassium current is made up of two components which differ in their sensitivity to 4‐aminopyridine (4‐AP) and tetraethylammonium (TEA). The component most sensitive to 4‐AP has fast activation kinetics and inactivates quickly at sustained depolarized voltages. By analogy with a current described in other preparations, this current was called IA. The component most sensitive to TEA has slower activation kinetics and inactivates more slowly at sustained depolarized voltages. This current was called IK. IA and IK were already present in neurones cultured for 24 h. The ratio between the peak of IK and that of IA increased significantly between 24 h and 4 days in culture. This means that the two components of the voltage‐dependent potassium current follow a different time course during development.
Prepartum milking and the onset of secretion of milk fat in the goat.
Authors: Brownhill J , Stewart H J , Thompson G E
Published: December 2014

Late‐pregnant goats were separated into two groups. A control group of four goats had small (approximately 3 ml) volumes of secretion expelled from one mammary gland at infrequent intervals between day 130 of gestation and parturition. An experimental group of five goats had as much secretion as possible removed from both glands twice daily beginning on day 137 of gestation and continuing until parturition. After parturition, both groups were milked twice daily. Regular 'milking out' before parturition stimulated secretion of triglyceride by the mammary gland, and most of the fatty acids secreted in the triglyceride before parturition had a chain length of 18 carbons. Secretion of 6‐14‐carbon chain‐length fatty acids in the milk triglycerides increased after parturition. There was no evidence that the onset of secretion of medium‐chain and long‐chain fatty acids occurred at different times in the control animals. It is concluded that the onset of secretion of medium‐chain and long‐chain fatty acids in milk triglycerides can be dissociated, although both are normally synchronized with parturition. Removal of secretion by the offspring at parturition may be a stimulus for the onset of secretion of long‐chain fatty acids, but the onset of secretion of medium‐chain fatty acids is brought about by some other mechanism.
Gamma‐aminobutyric acid uptake and the termination of inhibitory synaptic potentials in the rat hippocampal slice.
Authors: Dingledine R , Korn S J
Published: December 2014

Intracellular recordings were made from CA1 pyramidal cells in the rat hippocampal slice to study the processes that influence the time course of inhibitory post‐synaptic potentials (i.p.s.p.s) mediated by gamma‐aminobutyric acid (GABA), and conductance changes evoked by ionophoretically applied GABA. The GABA‐uptake inhibitors, nipecotic acid and cis‐4‐OH‐nipecotic acid (1 mM), greatly prolonged conductance increases associated with both hyperpolarizing and depolarizing responses to ionophoretically applied GABA. In contrast to their effects on GABA‐evoked conductances, uptake inhibitors only slightly prolonged antidromically evoked i.p.s.p.s. Their primary effect occurred after the i.p.s.p. had decayed to 5‐30% of its peak. 4‐OH‐isonipecotic acid, a nipecotic acid analogue that does not inhibit GABA uptake, did not prolong i.p.s.p.s or ionophoretically evoked conductance changes. Sodium pentobarbitone (100 microM), a drug that prolongs the open time of GABA‐activated chloride channels, potentiated both i.p.s.p.s and responses to ionophoretically applied GABA. Whereas pentobarbitone also prolonged i.p.s.p.s, it did not prolong responses to ionophoretically applied GABA. The prolongation of i.p.s.p.s by pentobarbitone occurred equally in both the early and late phases of the i.p.s.p., in contrast to the effects of GABA‐uptake inhibitors. I.p.s.p.s did not usually decay exponentially. The observation that uptake inhibitors prolonged the late but not the early decay phase of the i.p.s.p., together with the previous finding that the conductance change persists for the duration of the i.p.s.p., indicate that GABA is present in the synapse throughout much of the i.p.s.p. These data suggest that diffusion of GABA out of the synapse, a non‐exponential process, is an important determinant of the i.p.s.p. decay time course. Increasing the extracellular potassium concentration from 3.5 to 8.5 mM resulted in spontaneously occurring, synchronous burst firing of pyramidal cells. Cis‐4‐OH‐nipecotic acid significantly reduced the number and amplitude of extracellularly recorded population spikes within each burst. We conclude that diffusion, channel open time and GABA uptake all influence the time course of GABA‐mediated i.p.s.p.s. The time course of a single, brief i.p.s.p. is determined predominantly by post‐synaptic channel kinetics and diffusion of GABA out of the synapse, whereas the inhibition produced by prolonged synaptic bursts or relatively long application of exogenous GABA can be markedly influenced by GABA uptake.(ABSTRACT TRUNCATED AT 400 WORDS)
The effect of intraluminal tryptophan and phenylalanine on small intestinal motility in the conscious dog.
Authors: Bull J S , Grundy D , Scratcherd T
Published: December 2014

The effect of D‐ and L‐isomers of tryptophan and phenylalanine on fasting motor activity of canine jejunum were investigated. Only L‐tryptophan had any effect on jejunal motility. The concentration of L‐tryptophan required to elicit a motor effect in 50% of animals was estimated at 28 mM. 50 mM‐L‐tryptophan stimulated jejunal motility after a latency of 4.5 +/‐ 0.7 min. The pattern of motility was similar to that evoked by feeding but continued for only 41 +/‐ 5 min and failed to disrupt the normal timing of the interdigestive migrating motor complex (m.m.c.). The duration of the subsequent phase II of the complex was, however, significantly reduced. Multiple infusion of L‐tryptophan also failed to disrupt the timing of the m.m.c. These data are consistent with the hypothesis that specific breakdown components of protein digestion are implicated in the stimulation of postprandial motor activity. The mechanisms involved in the motor response to L‐tryptophan are discussed.
On the neurotrophic control of acetylcholine receptors at frog end‐plates reinnervated by the vagus nerve.
Authors: Brenner H R , Micheroli R
Published: December 2014

To test whether the properties of subsynaptic acetylcholine (ACh) receptors in skeletal muscle fibre are influenced by the type of the innervating neurone some pharmacological properties of ACh receptor in normal end‐plates and in denervated end‐plates reinnervated by the vagus nerve in the frog were compared. Blockade of nerve‐evoked synaptic currents by 200 microM‐hexamethonium was stronger at vagus‐reinnervated than at normal end‐plates. Blockade at both types of junctions was voltage dependent. The effect of hexamethonium on equilibrium currents induced by bath‐applied ACh and carbamylcholine was similar at the two types of junctions. At both normal and vagus‐reinnervated junctions, decamethonium had similar partial agonist properties. Following a step in membrane potential, the relaxations of ACh‐induced conductance changes at the two types of junctions were affected in a similar fashion by hexamethonium: hyperpolarization first produced a fast decrease and then a slow exponential increase in conductance. Upon depolarization, a fast increase was followed by an exponential decline to its original level. The time constant of the slow relaxation was slightly prolonged compared to control. These findings are consistent with a fast blocking action of open channels by hexamethonium. The effectiveness of hexamethonium in blocking end‐plate currents was reduced in the presence of (+)‐tubocurarine, indicating that hexamethonium has a competitive blocking action on the receptors. These results do not indicate that the pharmacological properties of the ACh receptors are changed after an end‐plate is reinnervated by a preganglionic neurone. The differential effect of hexamethonium on transmission at normal and vagus‐reinnervated end‐plates is discussed as a consequence of different transmitter release characteristics at the two types of junctions.
Caudal medullary expiratory neurone and internal intercostal nerve discharges in the cat: effects of lung inflation.
Authors: Cohen M I , Feldman J L , Sommer D
Published: December 2014

In midcollicular decerebrate, thoracotomized, paralysed cats that were ventilated by a cycle‐triggered pump and had an expiratory load, recordings were taken from expiratory neurones in the nucleus retroambigualis of the caudal medulla and from the internal intercostal nerves at T8‐T9 levels. Expiratory neurone and internal intercostal activities had augmenting patterns of two types: (a) step‐ramp (one‐third of the neurones): a large initial increase of activity synchronous with inspiratory termination, followed by a ramp increase throughout the expiratory phase; (b) ramp (two‐thirds of the neurones): a steady rise of activity without a sharp initial increase, discharge usually starting after a delay (as much as several hundred milliseconds) from the onset of expiration. Both types of unit pattern could occur together with each type of internal intercostal pattern. At the end of expiration, unit activity shut off abruptly just prior (0‐120 ms) to the onset of phrenic discharge. The effects of pulmonary afferent discharge on unit and internal intercostal activities were evaluated by use of inflation tests: withholding inflation during the preceding inspiratory phase; maintaining inflation at the end‐inspiratory level during expiration. Both tests produced lengthening of expiratory phase duration (TE), but their effects on activity differed. Following no‐inflation during inspiration, the discharge onset delay was lengthened for most ramp neurones, but for only a minority of step‐ramp neurones; the slope of activity augmentation did not change on the average; and the peak (end‐expiratory) discharge frequency was only slightly increased. The predominant effect of maintained expiratory inflation was reduction of activity slope for ramp neurones and for a minority of step‐ramp neurones, as well as increase of peak frequency; there was a moderate increase of discharge onset delay for ramp neurones, but not for step‐ramp neurones. The lengthening of TE produced by no‐inflation in the preceding inspiration was associated with lengthening of the durations of both the discharge onset delay and the discharge burst, but there was no correlation between changes of these two variables. We observed a 'reversal phenomenon': moderate inflation facilitated activity, whereas higher inflation levels depressed activity, as demonstrated by: comparison of effects of maintained expiratory deflation (removal of the expiratory load) and of maintained expiratory inflation, both of which reduced activity; comparison of effects of phasic expiratory inflations having different magnitudes.(ABSTRACT TRUNCATED AT 400 WORDS)
The long‐term excitability of myelinated nerve fibres in the transected frog sciatic nerve.
Authors: Wang G K
Published: December 2014

The long‐term excitability and the ionic currents in the nodes of Ranvier were studied in the severed frog sciatic nerve and the unoperated contralateral control nerve. After unilateral nerve section, compound action potentials of the nerve bundles and action potentials of single myelinated nerve fibres remained normal in amplitude and duration in either sciatic nerve for more than 38 days when frogs were kept at 11 degrees C. During this period the resting potentials averaged about ‐75 mV. Under voltage‐clamp conditions Na currents and K currents in transected single myelinated nerve fibres also appeared normal in their kinetics, and in their peak amplitudes. These results indicate that the Na‐ and K‐channel densities are quantitatively unchanged after the nerve transection, up to several weeks. The excitability of the severed sciatic nerve, expectedly, depends strongly on the time course of Wallerian degeneration. When frogs were kept at room temperature, the nerve excitability remained normal for only about 8‐10 days, due to the faster Wallerian degeneration; whereas at 4 degrees C it was maintained for more than 84 days, as long as the myelinated nerve fibres did not degenerate. Together, these findings demonstrate that Na channels, K channels, and Na‐K pumps are continuously present for several weeks in the transected nerve before nerve degeneration. It is surmised that either, (a) these proteins are extremely stable in the transected myelinated nerve fibres, or (b) they are supplied locally by Schwann cells, an open question recently posed by Chiu, Schrager & Ritchie (1984). In either event, the myelinated nerve fibres do not require cell bodies to provide a significant amount of new channels and pumps in order to retain their long‐term excitability.
Ionic conductances in frog short skeletal muscle fibres with slow delayed rectifier currents.
Authors: Lynch C
Published: December 2014

Short (0.8‐1.6 mm) lumbricalis fibres of Rana pipiens were voltage clamped by a two‐micro‐electrode technique at 5 degrees C in sucrose hypertonic Ringer solution (SHR). Terminated linear cable analysis suggests that if the current electrode is placed near the centre of the fibre length and the voltage‐sensing electrode is placed 0.19 times the fibre length from the current electrode, the fibre can be adequately voltage clamped and the conductance may be simply calculated as I/V for fibre length constants from 1.0 to 0.15 mm. In SHR solution lumbricalis fibres have action potentials with peak amplitudes of only +2 to 7 mV and a slow, gradual repolarization, distinct from the action potentials observed in sartorius muscle. In 60 mM‐Na+ SHR the inward Na current could be adequately controlled over the fibre length, providing an estimated Na conductance (GNa) of 8.9 mS/cm2. The magnitude of GNa and GK (delayed rectifier) in lumbricalis fibres was approximately 20% of that reported for sartorius and semitendinosus, although the resting conductances were similar. Fibres demonstrated delayed rectifier currents with complex patterns of activation suggesting two components of conductance (fast, GK,f and slow, GK,s) which were combined together in varied amounts: (a) GK,f activated rapidly to a maximum within 80 ms at 0 mV as previously described (Adrian, Chandler & Hodgkin, 1970a); (b) GK,s activated gradually with depolarizations below ‐50 mV and achieving peak currents at about 400 ms at 0 mV. In about 10% of lumbricalis fibres studied, GK,s occurred in isolation with a peak magnitude of 1.4 +/‐ 0.4 mS/cm2 (+/‐ S.D.). GK,s activation kinetics and tail currents are described by a squared two‐state (l2) Hodgkin‐Huxley model and have a Q10 of 2.8. These currents inactivated with a time constant of 5‐7 s at 0 mV. Isolated GK,s with identical kinetics was also observed in certain sartorius fibres studied with the three‐electrode voltage clamp. The fractional amount of GK,s in the combined delayed rectifier (GK,s + GK,f) currents could be estimated from analysis of the late activation phase with depolarization. Combined delayed currents were described by summing GK,f currents using a n4 model with GK,s currents defined by the l2 model.
Direct observations of responses of mesenteric microcirculation of the rat to circulating noradrenaline.
Authors: Hébert M T , Marshall J M
Published: December 2014

The responses of mesenteric microcirculation of the rat to circulating noradrenaline were studied by in vivo microscopy, using a photo‐electric device placed on a television monitor to measure changes in diameter of individual vessels. Blood flow was measured in the anterior mesenteric artery with an electromagnetic flow transducer, mesenteric vascular conductance was computed on‐line from mesenteric artery flow and arterial pressure. I.V. injection of noradrenaline induced a decrease in diameter of arterioles (less than 30 microns) which began simultaneously with the rise in arterial pressure and averaged 15% at 15‐20 s. By contrast small and principal arteries (30‐40 microns and 80‐350 microns respectively) generally showed a diameter increase which averaged 10% and began at the peak of the pressor response. Venules and veins (12‐560 microns) showed a diameter decrease which averaged 12‐15% at 25‐30 s. Meanwhile mesenteric vascular conductance fell by 65‐75% in 10 s and rose to 30‐50% above control in 25‐30 s. The diameter increases of small and principal arteries were not reflex dilator responses initiated by the rise in systemic arterial pressure, nor due to beta‐adrenoreceptor stimulation. However, local application of phentolamine abolished responses of all sections of the vascular tree indicating that they all depended on activation of alpha‐adrenoreceptors. During I.V. infusion of noradrenaline small arteries showed a maintained increase in diameter which began at the peak of the pressor response, while arterioles initially decreased in diameter but then relaxed, often attaining resting diameter before infusion ceased. Meanwhile mesenteric flow and conductance decreased transiently, but then returned to near control levels, i.e. 'autoregulatory escape' occurred. It is argued that noradrenaline induced alpha‐mediated contraction of all sections of the vascular tree; the tendency of arteries to constrict was counteracted by the rise in intravascular pressure caused by arteriolar constriction, active constriction of venous vessels may have been augmented by passive collapse secondary to arteriolar constriction. The secondary relaxation of arterial vessels reflects an inherent property of their smooth muscle to relax from the constrictor influence of noradrenaline and is more marked in proximal than distal vessels. It is proposed that the initial decrease in mesenteric vascular conductance in response to circulating noradrenaline may be attributed to active constriction of distal arterioles and the secondary increase in conductance ('escape') to secondary relaxation of more proximal arterial vessels.
Autoregulation of hind‐limb blood flow in conscious dogs.
Authors: Britton S L , Metting P J , Ronau T F , Strader J R , Weldy D L
Published: December 2014

We evaluated the efficiency of blood flow autoregulation of the hind‐limb vascular bed of eleven conscious dogs during: resting conditions; graded levels of treadmill exercise; and increases in oxygen consumption produced by the administration of 2,4‐dinitrophenol (DNP). Blood flow to the left hind limb was measured with an electromagnetic flow probe on the left external iliac artery. Hind‐limb perfusion pressure was measured from a catheter in the deep femoral artery and was controlled via an externally inflatable occlusion cuff positioned just distal to the flow probe. Arterial pressure was measured in the abdominal aorta. Experiments were performed 5‐16 days after instrumentation. Hind‐limb pressure‐flow (P‐F) relationships were evaluated by decreasing hind‐limb perfusion pressure in 4‐5 small sequential 'square‐wave' steps of 10‐15 mmHg each while measuring flow. Each step decrease in perfusion pressure was maintained for 2 min. The efficiency of autoregulation was quantified by calculating the closed‐loop gain of flow regulation (Gc) at each decrement in perfusion pressure utilizing the equation: Gc = 1‐[(F0‐Fn/F0)/(P0‐Pn/P0)] where F0 and P0 are the starting (control) flows and pressures prevailing prior to decreasing perfusion pressure, and Fn and Pn are the new flows and pressures at each decrement in perfusion pressure. A Gc value less than 0 indicates a predominantly passive P‐F relationship, while a Gc of 1 is perfect autoregulation of flow. When the dogs were at rest, decrements in hind‐limb perfusion pressure were accompanied by almost equivalent decreases in flow, i.e. no autoregulation occurred, and Gc averaged ‐0.177 +/‐ 0.044 over the pressure range from 100‐40 mmHg. During all levels of treadmill exercise (on gradients of 0, 7, or 21%), however, positive Gc values were found that averaged from 0.258 +/‐ 0.046 at a gradient of 0% to 0.392 +/‐ 0.041 at a gradient of 21% and were significantly different from Gc values found during rest at perfusion pressure ranges from 90‐40 mmHg. The administration of DNP directly into the hind‐limb circulation increased hind‐limb blood flow from 199 to 481 ml/min. In the presence of DNP, Gc values were positive over perfusion pressure ranges from 100‐40 mmHg and averaged 0.473 +/‐ 0.054. These data demonstrate that hind‐limb blood flow is not autoregulated in resting dogs, but that significant autoregulation is manifest during conditions that increase oxygen consumption.(ABSTRACT TRUNCATED AT 400 WORDS)
Muscarinic M1 and M2 receptors mediate depolarization and presynaptic inhibition in guinea‐pig enteric nervous system.
Authors: North R A , Slack B E , Surprenant A
Published: December 2014

Intracellular recordings were made from guinea‐pig myenteric and submucous plexus neurones. Nicotinic excitatory post‐synaptic potentials (fast e.p.s.p.s) and slow e.p.s.p.s were recorded in both plexuses; adrenergic inhibitory post‐synaptic potentials (i.p.s.p.s) were recorded from submucous plexus neurones. The effects of muscarinic agonists and antagonists were examined on the synaptic potentials in those neurones in which these substances did not change the membrane potential. Muscarine, oxotremorine, methylfurmethide and McNeil A343 reversibly depressed the amplitude of the fast e.p.s.p. in a concentration‐dependent way. Hyoscine, pirenzepine and 4‐diphenylacetoxy‐N‐methyl‐piperidine (4‐DAMP) caused a parallel shift to the right of the agonist dose‐response curves. These muscarinic antagonists themselves did not alter the amplitudes of fast e.p.s.p.s evoked by low frequency (0.05‐0.1 Hz) stimulation. Antagonist pA2 values (the negative logarithm of the dissociation equilibrium constant) were determined while recording from individual neurones. pA2 values were: pirenzepine 7.0, hyoscine 8.9, and 4‐DAMP 8.7. I.p.s.p.s in the submucous plexus were also depressed by muscarinic agonists, and this was competitively reversed by pirenzepine and 4‐DAMP, with apparent pA2 values of 6.9 and 8.7 respectively. Muscarinic antagonists alone increased the amplitude of the i.p.s.p. evoked either by single or repeated stimuli. This enhancement was observed with low concentrations of antagonists and did not become greater when the concentrations were increased. Muscarinic agonists depolarized about one‐quarter of myenteric and submucous plexus neurones. Low concentrations of pirenzepine antagonized these depolarizations; the pA2 value was 8.4. Cholinergic slow e.p.s.p.s recorded in some myenteric neurones were depressed or abolished by pirenzepine; concentrations that caused 50% inhibition (IC50) for this action ranged from 10 to 60 nM. It is concluded that presynaptic muscarinic receptors, activation of which inhibits the release of acetylcholine and noradrenaline, are the m2 type. Post‐synaptic muscarinic receptors, activation of which depolarizes the membrane, are of the m1 type. The results also suggest that acetylcholine may exert a tonic inhibition of noradrenaline release in the submucous plexus through m2 receptors, and mediates the slow e.p.s.p. in the myenteric plexus through m1 receptors.
Refractive sectors in the visual field of the pigeon eye.
Authors: Fitzke F W , Hayes B P , Hodos W , Holden A L , Low J C
Published: December 2014

Scheiner's principle has been used in electroretinographic optometry to refract the photoreceptor plane in different regions of the visual field of the pigeon eye. Along the horizon and in the upper visual field the eye is emmetropic, or nearly so. Below the horizon the eye becomes progressively more myopic at more negative elevations, refractive state falling to ‐5D at ‐90 deg. Lower field myopia is not an artifact of oblique astigmatism, nor of an aberration symmetrical about the optical axis. It is suggested that lower field myopia is a biological adaptation suited to keep the photoreceptors in the upper retina conjugate with the ground. Refractive state below the horizon can be fitted with a sine function by varying a parameter H (eye‐ground height). The value of H agrees well with directly measured eye‐ground height.
Pathway to the cerebral cortex for impulses from tendon organs in the cat's hind limb.
Authors: McIntyre A K , Proske U , Rawson J A
Published: December 2014

In cats anaesthetized with alpha‐chloralose, extracellular, recordings were made from neurones lying in nucleus Z. All cells could be excited by electrical stimulation of ipsilateral hind‐limb muscle nerves at group I strength. Many cells showed an irregular background discharge. In response to graded contraction of hind‐limb muscles, including lateral gastrocnemius, soleus and flexor digitorum longus, cell discharge changed in a manner suggesting that it was driven by input from muscle spindles or from tendon organs. Responses of individual nucleus Z cells were always specific to one kind of receptor and there was no evidence of convergence of afferent impulses from spindles and tendon organs. Nucleus Z neurones excited by muscle group I input could be antidromically driven by stimulation of the contralateral thalamus identifying them as bulbo‐thalamic projection neurones. The same cells could be driven trans‐synaptically by stimulation of the ipsilateral anterior lobe of the cerebellum. It was possible using a collision test to show that afferent fibres synapsing on nucleus Z cells were collaterals of dorsal spinocerebellar tract cells. It is concluded that nucleus Z is a brain stem relay for afferent information from muscle spindles and tendon organs which is destined for the cerebral cortex.
A comparison of visual responses of cat lateral geniculate nucleus neurones with those of ganglion cells afferent to them.
Authors: Cleland B G , Lee B B
Published: December 2014

We compared visual responses of cat lateral geniculate nucleus (l.g.n.) neurones with those of retinal ganglion cells providing their afferent inputs. Quantitative studies were made on twenty such pairs; eight X on‐centre, seven Y on‐centre, two X off‐centre and three Y off‐centre pairs. Receptive field centre locations of cell pairs with correlated activities were very closely superimposed, having a mean centre displacement of 1.6 minutes of arc for X cells and 11 minutes of arc for Y cells. With flashed spots and annuli, responses of l.g.n. cells were almost always smaller than those of their retinal afferents, with peaks and troughs in ganglion cell responses being faithfully followed in the geniculate neurones. This is consistent with almost all impulses from the l.g.n. cell being triggered by the afferent feeding its centre. With spots of different sizes and contrasts, modulation of responses by l.g.n. inhibition was obvious, but effects were complex. With moving bright‐bar stimuli, although response histograms were clearly reshaped to some extent in the l.g.n., peak firing rates under different stimulus conditions were often merely attenuated by a constant factor for most l.g.n. cells in comparison with their retinal inputs. For velocity tuning curves, a few cell pairs showed selective attenuation at high speeds, while others showed it at low speeds. All the latter group appeared to have more than one major excitatory afferent. These changes in velocity tuning occurred across the X/Y classification, so that differences in velocity preference of the X and Y systems is more blurred in the l.g.n. than in the retina.
Gastrin response to a meal before and after cutting the extrinsic nerves of the stomach in the dog.
Authors: Eysselein V E , Niebel W , Singer M V
Published: December 2014

Atropine inhibits the post‐prandial gastrin release after truncal vagotomy in the dog. Whether this action of atropine is due to suppression of stimulatory cholinergic fibres in the sympathetic nerves of the stomach and the upper small intestine or due to blockade of intrinsic gastric cholinergic mechanisms is unknown. Conscious dogs were fed a meat meal (35 g/kg body weight) before and after truncal vagotomy and after truncal vagotomy plus coeliac and superior mesenteric ganglionectomy. Experiments were repeated in the presence of atropine (50 micrograms/kg body weight, given as an i.v. bolus 60 min prior to the meal). In another set of dogs, only ganglionectomy was performed and the same experiments were done as in the first set of dogs. Truncal vagotomy enhanced the post‐prandial 120 min integrated plasma gastrin response by 2.6 times as compared to the response with the vagus nerves intact. Before truncal vagotomy, atropine enhanced the integrated plasma gastrin response by 2.6 times; after truncal vagotomy atropine suppressed this response by 2.3 times. After truncal vagotomy, with or without atropine, additional coeliac and superior mesenteric ganglionectomy did not alter the integrated plasma gastrin response. With the vagus nerves intact, ganglionectomy alone had no effect on the integrated plasma gastrin response whether or not atropine was given. The finding that atropine suppresses the post‐prandial plasma gastrin response to a meal after truncal vagotomy and coeliac and superior mesenteric ganglionectomy, i.e. cutting the extrinsic nerves of the stomach and the upper small intestine, suggests the existence of stimulatory cholinergic intrinsic fibres located within the stomach.
Adenosine increases synaptic facilitation in the in vitro rat hippocampus: evidence for a presynaptic site of action.
Authors: Dunwiddie T V , Haas H L
Published: December 2014

The effect of adenosine on paired synaptic responses was characterized in the CA1 region of the rat hippocampus in vitro. Adenosine increased the degree of synaptic facilitation at a 40 ms conditioning‐testing interval under all conditions tested. Even when the stimulation intensity was increased so as to counteract the direct depressant effect of adenosine on synaptic transmission, its effect on facilitation was maintained. The ability of adenosine to increase synaptic facilitation was a complex function of several variables. The effect was enhanced by increasing the calcium concentration of the medium, and was most pronounced at short conditioning‐testing intervals and at low response amplitudes. Adenosine was particularly efficacious in blocking the depression of synaptic responses observed in high‐calcium medium at short conditioning‐testing intervals. Because this depression most probably reflects depletion of the available store of releasable transmitter, one mechanism by which adenosine could reverse this effect would be by blocking the depletion of transmitter. These results suggest that adenosine diminishes transmitter release via an action at the presynaptic terminal. The reduction in the release of neurotransmitter, particularly at excitatory synapses, may be responsible for the depressant effects of adenosine upon the central nervous system.
Partitioning of monosynaptic Ia excitatory post‐synaptic potentials in the motor nucleus of the cat semimembranosus muscle.
Authors: Hamm T M , Koehler W , Stuart D G , Vanden Noven S
Published: December 2014

In anaesthetized low‐spinal cats, intracellular recordings were made of the Ia excitatory post‐synaptic potential (e.p.s.p.) responses of semimembranosus motoneurones to electrical stimulation (Group I range) of nerve branches supplying the anterior and posterior heads of semimembranosus, the anterior and posterior parts of biceps femoris, and the distal part of semitendinosus. Recordings were also made during stimulation of nerves to the gracilis muscle and to the vasti muscle group. Stimulation of the semimembranosus‐anterior nerve branch produced Ia e.p.s.p.s. of greater amplitude in semimembranosus‐anterior motoneurones than in semimembranosus‐posterior cells; likewise, stimulation of the semimembranosus‐posterior nerve branch produced larger e.p.s.p.s. in cells which supplied the posterior head than in those which supplied the anterior head. Stimulation of the nerve branches to components of two 'flexor' muscles (Sherrington, 1910), biceps‐posterior and semitendinosus‐distal, produced larger e.p.s.p.s in semimembranosus‐posterior cells than in the anterior motoneurones. A tendency was found for stimulation of the nerve to biceps femoris‐anterior (an 'extensor') to produce larger e.p.s.p.s in semimembranosus‐anterior than in‐posterior motoneurones. However, this effect was of borderline (0.06 greater than P greater than 0.05) significance. The limited monosynaptic input produced by stimulation of the nerves to the gracilis and vasti muscles showed that their Ia axons do not distinguish between the two semimembranosus cell groups. A slight topographic organization of motoneurones within the semimembranosus motor nucleus was found, with anterior cells encountered, on average, at a more rostral level of the spinal cord than posterior cells. A similar topographic arrangement was observed in the rostrocaudal distribution of Group I afferent fibres in the dorsal roots and motor axons from the two sets of motoneurones in the ventral roots. These findings are consistent with 'location specificity' (Scott & Mendell, 1976) being a factor which contributes to the observed pattern of homonymous Ia connexions. A role for 'species specificity' (Scott & Mendell, 1976) in determining the observed pattern of homonymous Ia connexions was indicated by species‐dependent differences in e.p.s.p. amplitude in pairs of semimembranosus‐anterior and ‐posterior motoneurones at similar rostrocaudal locations in the spinal cord. The pattern of heteronymous connexions to the semimembranosus motor nucleus also showed evidence for species specificity. However, no clear topographic pattern was evident in these connexions.
Fast events in single‐channel currents activated by acetylcholine and its analogues at the frog muscle end‐plate.
Authors: Colquhoun D , Sakmann B
Published: December 2014

The fine structure of ion‐channel activations by junctional nicotinic receptors in adult frog muscle fibres has been investigated. The agonists used were acetylcholine (ACh), carbachol (CCh), suberyldicholine (SubCh) and decan‐1,10‐dicarboxylic acid dicholine ester (DecCh). Individual activations (bursts) were interrupted by short closed periods; the distribution of their durations showed a major fast component ('short gaps') and a minor slower component ('intermediate gaps'). The mean duration of both short and intermediate gaps was dependent on the nature of the agonist. For short gaps the mean durations (microseconds) were: ACh, 20; SubCh, 43; DecCh, 71; CCh, 13. The mean number of short gaps per burst were: ACh, 1.9; SubCh, 4.1; DecCh, 2.0. The mean number of short gaps per burst, and the mean number per unit open time, were dependent on the nature of the agonist, but showed little dependence on agonist concentration or membrane potential for ACh, SubCh and DecCh. The short gaps in CCh increased in frequency with agonist concentration and were mainly produced by channel blockages by CCh itself. Partially open channels (subconductance states) were clearly resolved rarely (0.4% of gaps within bursts) but regularly. Conductances of 18% (most commonly) and 71% of the main value were found. However, most short gaps were probably full closures. The distribution of burst lengths had two components. The faster component represented mainly isolated short openings that were much more common at low agonist concentrations. The slower component represented bursts of longer openings. Except at very low concentrations more than 85% of activations were of this type, which corresponds to the 'channel lifetime' found by noise analysis. The frequency of channel openings increased slightly with hyperpolarization. The short gaps during activations were little affected when (a) the [H+]o or [Ca2+]o were reduced to 1/10th of normal, (b) when extracellular Ca2+ was replaced by Mg2+, (c) when the [Cl‐]i was raised or (d) when, in one experiment on an isolated inside‐out patch, the normal intracellular constituents were replaced by KCl. Reduction of [Ca2+]O to 1/10 of normal increased the single‐channel conductance by 50%, and considerably increased the number of intermediate gaps. No temporal asymmetry was detectable in the bursts of openings. Positive correlations were found between the lengths of successive apparent open times at low SubCh concentrations, but no correlations between burst lengths were detectable. The component of brief openings behaves, at low concentrations, as though it originates from openings of singly occupied channels.(ABSTRACT TRUNCATED AT 400 WORDS)
Excitation of neurones in the rat paraventricular nucleus in vitro by vasopressin and oxytocin.
Authors: Inenaga K , Yamashita H
Published: December 2014

Extracellular recordings were made from ninety‐seven spontaneously firing cells in the paraventricular nucleus (p.v.n.) of the rat hypothalamic slice preparation. The spontaneously firing cells tested fired at 0.1‐8 spikes/s but the majority showed a slow irregular firing pattern. The average firing rate of all ninety‐seven cells was 2.2 +/‐ 0.2 spikes/s (mean +/‐ S.E. of mean). Six cells showed a phasic firing pattern. Following bath application of arginine‐vasopressin (AVP) 10(‐7) M, sixty‐four (66%) of ninety‐seven p.v.n. cells showed excitatory responses and three (3%) cells inhibitory responses. Bath application of oxytocin (OXT) 10(‐7) M excited thirty‐nine (57%) of sixty‐eight p.v.n. cells and inhibited two (3%) cells. Individual p.v.n. cells responded to application of both AVP and OXT, but the magnitude and threshold of the responses varied from cell to cell. Of the sixty‐six cells tested with both peptides at 10(‐7) M, sixteen showed similar responses to both and fifteen showed no response to either: twenty cells showed a greater response to AVP and fifteen a greater response to OXT. Of six phasic firing cells, two showed excitatory responses to AVP and all four cells tested did not show any response to OXT. The dose‐dependence of the response to AVP and OXT was tested in six p.v.n. cells. There was a direct relationship between peptide concentration and increased firing rate. The threshold concentration of the peptides ranged from 10(‐8) to 10(‐10) M. The cells responsive to the peptides were not located in particular areas of the p.v.n. but were diffusely distributed throughout the nucleus. After blocking synaptic transmission with a low Ca2+ and high Mg2+ medium, all tested cells (AVP, n = 15; OXT, n = 14) which had responded to applications of AVP or OXT in normal medium still showed responses to the peptides, although the effect was less marked in half the cells. However, in the absence of synaptic transmission two cells showed unimpaired responses to one of the peptides but greatly depressed responses to the other. The V1‐receptor antagonist [1‐(beta‐mercapto‐, beta‐cyclopentamethylenepropionic acid)], 8‐D‐arginine‐vasopressin (d(CH2)5DAVP) or V1/V2‐receptor antagonist [1‐(beta‐mercapto‐, beta‐cyclopentamethylenepropionic acid), 2‐D‐tyrosine,4‐valine]arginine‐vasopressin (d(CH2)5D‐TyrVAVP) completely or partly blocked the AVP‐induced responses, while the V2‐receptor agonist 1‐deamino‐8‐D‐arginine‐vasopressin (dDAVP) did not influence the spontaneous discharges of the cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Acetylcholine receptor activation by a site‐selective ligand: nature of brief open and closed states in BC3H‐1 cells.
Authors: Sine S M , Steinbach J H
Published: December 2014

Single‐channel currents were recorded through acetylcholine receptor channels of clonal BC3H‐1 muscle cells activated by the curare‐like compound, DMT binds selectively to the two alpha‐neurotoxin‐binding sites on these receptors, with apparent dissociation constants differing by about 1000‐fold (Sine & Taylor, 1981). Receptor channels do not open with DMT bound only to the high‐affinity site, but only at DMT concentrations at which both high‐ and low‐affinity sites are occupied. Open‐duration histograms are not single exponentials, but are described by the sums of two (or three) exponentials. Both brief‐ and long‐duration openings are observed in the presence of 3 microM‐DMT, and are seen at the same relative frequency up to 80 microM‐DMT. Long‐duration openings are interrupted by brief closures with a mean duration of 50 microseconds and which occur at a frequency of 50‐60 per second of open time. These temporal characteristics closely parallel those of the brief closures observed with the full agonists, acetylcholine, carbamylcholine, and suberyldicholine. Raised concentrations of DMT apparently block open channels in a voltage‐dependent fashion. It is concluded that both brief‐ and long‐duration openings arise from receptors with two molecules of DMT bound. Furthermore, brief closures in general do not appear to reflect receptor activation processes. Instead, they seem to arise through entry to a closed state with properties independent of the agonist, but characteristic of open channels.