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T C Muir

Publications and source records attributed to T C Muir.

At least 37 records · Page 2Linked to original sources
PubMed1985

Mechanisms underlying electrical and mechanical responses of the bovine retractor penis to inhibitory nerve stimulation and to an inhibitory extract.

The response of the bovine retractor penis (BRP) to stimulation of non-adrenergic, non-cholinergic (NANC) inhibitory nerves and to an inhibitory extract prepared from this muscle have been studied using intracellular microelectrode, sucrose gap and conventional mechanical recording techniques. Both inhibitory nerve stimulation and inhibitory extract hyperpolarized the membrane potential and relaxed spontaneous or guanethidine (3 X 10(-5) M)-induced tone. These effects were accompanied by an increase in membrane resistance. Following membrane potential displacement from an average value of -53 +/- 7 mV (n = 184; Byrne & Muir, 1984) inhibitory potentials to nerve stimulation were abolished at approximately -30 mV; there was no evidence of reversal. Displacement by inward hyperpolarizing current over the range -45 to -60 mV increased the inhibitory response to nerve stimulation and to inhibitory extract; at more negative potential values (above approximately -60 mV) the inhibitory potential decreased and was abolished (approximately -103 mV). There was no evidence of reversal. Removal of [K+]o reversibly reduced hyperpolarization to nerve stimulation and inhibitory extract. No enhancement was observed. Increasing the [K+]o to 20 mM reduced the inhibitory potential to nerve stimulation but this was restored by passive membrane hyperpolarization. Inhibitory potentials were obtained at membrane potential values exceeding that of the estimated EK (-49 mV). [Cl-]o-free or [Cl-]o-deficient solutions reduced and abolished (after some 20-25 min) the hyperpolarization produced by inhibitory nerve stimulation or inhibitory extract. The inhibitory potential amplitude following nerve stimulation was not restored by passive displacement of the membrane potential from -26 to -104 mV approximately. Ouabain (1-5 X 10(-5) M) reduced then (45-60 min later) abolished the inhibitory potential to nerve stimulation. The effects of this drug on the extract were not investigated. It is concluded that the inhibitory response to nerve stimulation and extract in the BRP may involve several ionic species. However, unlike that in gastrointestinal muscles the NANC response in the BRP is accompanied by an increased membrane resistance and does not primarily involve K+. The underlying mechanisms for the inhibitory response to both NANC nerve stimulation and inhibitory extract appear to be similar, compatible with the view that the latter may contain the inhibitory transmitter released from these nerves in this tissue.

Animals↗
PubMed1985

Mechanisms underlying the electrical and mechanical responses of the guinea-pig internal anal sphincter to field stimulation and to drugs.

The electrical membrane characteristics and the response of the circular muscle of the guinea-pig internal anal sphincter (i.a.s.) to field stimulation were studied in vitro using intracellular microelectrodes and conventional mechanical recording techniques. The i.a.s. developed its own tone (3-4 g), following initial stretch (1 g) and spontaneous spike potentials were evident. In the absence of spike potentials, tone declined and disappeared. Tone was not significantly reduced by phentolamine (1 X 10(-6)M). The resting membrane potential, measured between spontaneous spike potentials, was -45 +/- 3.0 mV (n = 224); the space constant (lambda) was 1.13 +/- 0.1 mm (n = 13). Spikes usually overshot by approximately 15 mV. The frequency of spike potential discharge (1-3 Hz) varied with the degree of membrane depolarization, being increased in K+-rich and decreased in K+-deficient solutions or by the presence of Mn2+. It was not significantly affected by C1-withdrawal but was increased in Na+-deficient solutions with or without tetrodotoxin (TTX; 1 X 10(-6)M). Field stimulation (1-20 Hz, 0.5 ms, supramaximal voltage) produced inhibitory junction potentials (i.j.ps) and relaxed tone; at high frequencies (50 Hz or greater), contractions were observed but excitatory junction potentials (e.j.ps) were not. I.j.ps and relaxations were inhibited by apamin (1 X 10(-6)M), TTX (1 X 10(-6)M) but not by atropine (1 X 10(-6)M), phentolamine (1 X 10(-6)M) or hexamethonium (1 X 10(-6)M). I.j.ps were reduced by hyperpolarization and enhanced by depolarization of the membrane by current pulses (15s). The mean equilibrium potential for the i.j.p. was -94 mV (correlation coefficient, gamma = 0.71, n = 5, p less than 0.001). I.j.ps were enhanced in K+-deficient solutions and reduced in K+-rich solutions. Together these results suggest that the i.j.p. is mediated by an increased GK. The absence of [Ca2+]o or the presence of Mn2+ (2 mM) abolished the i.j.p.; in contrast Na+-deficient or C1-free solutions were ineffective in this respect. Tetraethylammonium (5-50mM) abolished the i.j.p.; the accompanying relaxation was reduced by about 80%. The major aspect of the relaxation to nerve stimulation is mediated by membrane hyperpolarization.

Anal Canal↗
PubMed1984

Electrical and mechanical responses of the bovine retractor penis to nerve stimulation and to drugs.

The responses of the bovine retractor penis muscle to field stimulation of intramural nerves in vitro was investigated using micro-electrode and extracellular (sucrose gap) techniques. In the absence of tone single pulses or trains of stimuli (1-50 Hz 0.1-0.5 m.sec) produced e.j.p.s and a decrease in membrane resistance; spike potentials were not observed. E.j.p.s often small in amplitude (3-5 mV to single pulse) and accompanied by contractions in almost all preparations were noradrenergic, abolished by guanethidine (1-3 x 10(-5) M) and tetrodotoxin (3.5 x 10(-6) M) but not by prazosin (0.05 - 1.4 x 10(-6) M). Prazosin abolished the depolarization and contraction produced by added NA (0.02 - 2 x 10(-8) moles). TEA (10(-2) M) depolarized the membrane and initiated spontaneous activity; e.j.p.s and contractions were enhanced and prolonged but no spikes were observed. Atropine (0.5 x 10(-6) M) increased and physostigimine (1-5 x 10(-6) M) decreased e.j.p.s and contractions indicating a cholinergic regulatory component in the release of the excitatory transmitter. In the presence of tone, nerve stimulation produced i.j.p.s. and relaxations which were unaffected by apamin (5 x 10(-7) M), atropine (3 x 10(-6) M), guanethidine (3 x 10(-5) M), phentolamine (5 x 10(-6) M) and propranolol (4 x 10(-6) M) but were abolished by tetrodotoxin (3.5 x 10(-7) M) suggesting their mediation by non-adrenergic non-cholinergic (NANC) nerves. Sodium nitroprusside (10(-10) - 10(-8) moles), which increases cyclic GMP, also hyperpolarized the membrane and relaxed the BRP. Those responses and those to inhibitory nerve stimulation were antagonized by oxyhaemoglobin which inhibits guanylate cyclase. 2-O-propoxyphenyl-8-azapurin-6-one (M & B 22948 3-9 x 10(-6) M) which inhibits cGMP-specific phosphodiesterase, enhanced the relaxation but not the i.j.p. TEA (10(-2) M) initially depolarized the membrane potential and raised tone. In the sucrose gap inhibitory potentials were abolished; the mechanical relaxation was not and a small contractile component emerged. Electrical and mechanical inhibitory components in the bovine retractor penis may not be correlated.

Adrenergic alpha-Antagonists↗
PubMed1983

Microelectrode recording of the effects of agonists and antagonists on alpha-adrenoceptors on rat somatic nerve terminals.

The effects of apomorphine, catechol, clonidine, isoprenaline, (-)-and (+/-)-noradrenaline, phenylephrine, pyrogallol and xylazine were investigated on the frequency and amplitude of miniature endplate potentials (m.e.p.ps) and, with the exception of apomorphine, catechol and pyrogallol, on the amplitude of endplate potentials (e.p.ps) in the rat phrenic nerve diaphragm preparation. Clonidine, (-)-noradrenaline, phenylephrine and xylazine (each at 1.5 X 10(-5)M) increased m.e.p.p. frequency but not amplitude. The other drugs were ineffective, except isoprenaline (1.5 X 10(-5)M) which enhanced m.e.p.p. amplitude but not frequency. The increase in m.e.p.p. frequency was inhibited by phentolamine, prazosin and yohimbine (each 1.5 X 10(-9)M). Prazosin and yohimbine alone each reduced m.e.p.p. frequency but failed to abolish m.e.p.ps even at high concentrations (10(-3)M). Clonidine, (-)-noradrenaline, phenylephrine and xylazine (each 3 X 10(-6)M) enhanced e.p.p. amplitude; this enhancement was blocked by prazosin and by yohimbine (each 3 X 10(-6)M). In preparations fatigued by prolonged continuous nerve stimulation (5 Hz, 0.05 ms for 30 min), (-)-noradrenaline (3.3 X 10(-4)M) restored m.e.p.p. frequency. The results indicate that adrenoceptors on somatic nerve terminals interact with both alpha 1- and alpha 2-agonists and antagonists and show different characteristics from those at autonomic neuroeffector junctions. The alpha-adrenoceptors on somatic nerve terminals may have an ancilliary physiological role in influencing but not controlling transmitter release.

Adrenergic alpha-Antagonists↗
PubMed1983

The effect of clonidine on the response to stimulation of non-adrenergic non-cholinergic nerves in the guinea-pig urinary bladder in-vitro.

The effects of clonidine on the response of the guinea-pig urinary bladder detrusor muscle to stimulation of non-adrenergic non-cholinergic (NANC) nerves were investigated in-vitro. In tissues from both treated and chemically sympathectomized animals, in the presence of atropine (10(-5) M) to inhibit cholinergic responses, clonidine (10(-10)-10(-6) M) invariably enhanced the contractile response to NANC nerve stimulation at 2, 5, 10 and 20 Hz. The enhancement was not inhibited by yohimbine (10(-5) M), phentolamine (10(-5) M), or the histamine H1- or H2-receptor antagonists mepyramine (10(-6) M) or cimetidine (10(-5) M) respectively. Phentolamine (10(-5) M), like clonidine, enhanced the response to stimulation of NANC nerves at 2, 5, 10 and 20 Hz. Xylazine, another alpha 2-agonist, which, unlike both clonidine and phentolamine, is not a substituted 2-imidazoline compound, failed to enhance the response in the bladder to NANC nerve stimulation. The results suggest that clonidine enhances the response to NANC nerve stimulation, independently of its effects on alpha-adrenoceptors, by increasing the amount of NANC transmitter available.

Adenosine Triphosphate↗
PubMed1983

Peripheral sympathetic pathways to gastroduodenal region of the guinea pig.

The sympathetic pathways to the stomach and duodenum of the guinea pig were studied by electrical nerve stimulation and by gastric distension in vitro and in vivo. The in vitro preparation consisted of the stomach and duodenum connected by para-arterial nerves to the celiac plexus. Gastroduodenal motility was measured with intraluminal pressure catheters. Stimulation of splanchnic nerves resulted in inhibition of propulsive contractions of both the stomach and duodenum. Stimulation of the left gastric nerve inhibited the stomach but not the duodenum, and stimulation of the gastroduodenal nerve inhibited the duodenum only. When the gastroduodenal nerve was stimulated, excitatory postsynaptic potentials were elicited in 18% of the cells from which intracellular recordings were made in the celiac ganglia. When the stomach was distended to a pressure of 5-7 cmH2O, propulsive contractions in the duodenum stopped in 86% of the distensions in the in vivo preparations and in 62% of the distensions in the in vitro preparations. Section of the gastroduodenal nerve eliminated the distension-induced inhibition of duodenal propulsion in vitro. These experiments describe the efferent sympathetic pathways to the celiac plexus of the guinea pig and demonstrate reflex pathways to the celiac plexus that can mediate a gastroduodenal inhibitory reflex.

Animals↗
PubMed1981

The response of the rabbit rectococcygeus muscle to stimulation of extrinsic inhibitory nerves and to sympathomimetic drugs.

1 The effects of stimulating sympathetic or non-adrenergic non-cholinergic (NANC) nerves or of the addition of noradrenaline (NA) or isoprenaline (Iso) were investigated on carbachol-induced tone and on contractions produced by acetylcholine (ACh) and by pelvic nerve stimulation, in the rabbit rectococcygeus muscle.2 Each procedure reduced carbachol-induced tone; sympathetic and NANC nerve stimulation were equipotent but both were less effective than sympathomimetic drugs, of which Iso was the better. Both Iso and NA, but not sympathetic nerve stimulation, inhibited the contractions produced by pelvic nerve stimulation in a concentration-dependent manner. Against ACh-induced contractions, only Iso was effective. The effects of NANC nerve stimulation on the motor responses to pelvic nerve stimulation or to ACh were not investigated.3 The inhibitory effects of sympathetic nerve stimulation, of Iso and of NA were reduced by propranolol (3 x 10(-6) M) but unaffected by phentolamine (3 x 10(-5) M).4 In the presence of high (45 mM) concentrations of KCl, Iso and NA produced a concentration-dependent inhibition of tone that was antagonized by propranolol (3 x 10(-6) M).5 Methoxamine (4 x 10(-7) to 4 x 10(-5) M) and phenylephrine (5 x 10(-7) to 5 x 10(-5) M) which interact mainly with alpha(1)-adrenoceptors, produced only small, transient reductions in carbachol-induced tone which were subject to tachyphylaxis, unlike those produced by Iso and NA. These inhibitory effects were antagonized by phentolamine (3 x 10(-6) M) or azapetine (3 x 10(-6) M).6 Phenylephrine (5 x 10(-4) M) and high doses (3 x 10(-5) M or greater) of NA enhanced the contractile response to pelvic nerve stimulation and, on occasion, produced muscle contraction. These effects were antagonized by phentolamine (3 x 10(-6) M).7 These results suggest that inhibition of the rectococcygeus, a muscle which has no intramural nerve plexus, can be inhibited by stimulation of extrinsic NANC nerves, the transmitter for which is unknown and by sympathetic nerve stimulation via alpha- and beta-adrenoceptors located postsynaptically on the muscle. Excitatory alpha-adrenoceptors may also be present.

Acetylcholine↗
PubMed1981

The electrical basis for contraction and relaxation in canine fundal smooth muscle.

1. Mechanical and intracellular electrical activities were recorded simultaneously from canine fundal and antral smooth muscle preparations.2. Most fundal preparations displayed no spontaneous electrical or mechanical activity. The tissue had a space constant of 1.5 mm and a time constant of 189 msec and showed outward rectification in response to depolarizing current.3. Transmural nerve stimulation of fundal preparations demonstrated the presence of cholinergic excitatory and non-cholinergic, non-adrenergic inhibitory neural inputs to the tissue. The cholinergic nerve response consisted of a small, graded depolarization accompanied by a slow graded contraction; the inhibitory nerve response consisted of a graded hyperpolarization accompanied by a slow relaxation.4. The excitatory fundal nerve response was abolished or greatly diminished by D(600) and Mn(2+). D(600) and Mn(2+) also decreased basal tone. The inhibitory nerve response was unaffected by either agent.5. The excitatory nerve response in the fundus was contrasted with the excitatory nerve response in the antrum. In the fundus, stimulation of cholinergic motor nerves produced a depolarization which always produced a contraction. In the antrum, stimulation of cholinergic motor nerves between action potentials produced graded depolarizations of antral cells; however, there were no associated contractions. Stimulation of cholinergic motor nerves during spontaneous action potentials increased the amplitude and duration of the plateau phase of the action potential; this was associated with an augmentation of the spontaneous contractions.6. Voltage-tension curves were determined for antral and fundal preparations using K(+) depolarization as a means of controlling membrane potential. Antral preparations displayed a voltage threshold for contraction at a membrane potential approximately 30 m V positive to the resting potential. In cntrast, fundal resting potentials were at or more positive than their voltage thresholds.7. These differences in electromechanical coupling provide an explanation for the marked differences in the responses of fundal and antral smooth muscles to nerve stimulation and account for their physiologic function in vivo.

Acetylcholine↗
PubMed1979

The electrical responses of the rabbit rectococcygeus following extrinsic parasympathetic nerve stimulation.

1. The responses of the rabbit rectococcygeus muscle to stimulation of the extrinsic pelvic nerves have been investigated using intracellular micro-electrode recording techniques. 2. Submaximal pelvic nerve stimulation evoked a depolarization (e.j.p.) which was graded with stimulus strength and abolished by atropine (10(-6) g/ml.) and tetrodotoxin (TTX). 3. Single supramaximal stimuli evoked action potentials associated with muscle contraction. 4. In the presence of atropine, to abolish the e.j.p.s, supramaximal stimulation of the pelvic nerves evoked hyperpolarizations (i.j.p.s) which were graded with stimulus strength and abolished by TTX. 5. The transmitter responsible for the i.j.p.s is unknown. Phentolamine (10(-5) g/ml.) and propranolol (3 x 10(-5) g/ml.) in concentrations which block respectively alpha and beta adrenoceptors and the adrenergic neurone blocking agent guanethidine (10(-6) g/ml.) were ineffective in blocking the inhibitory response. 6. It is concluded that stimulation of the pelvic nerves to the rectococcygeus releases two transmitters, acetylcholine, responsible for the e.j.p. (and muscle contraction) and a non-adrenergic non-cholinergic transmitter which is the basis for the mechanical relaxation.

Animals↗
PubMed1978

Effects of end-tidal concentrations of cyclopropane, halothane and diethyl ether on peripheral autonomic neuroeffector systems in the rat.

The effects of the inhalation anaesthetics, cyclopropane, halothane and diethyl ether were examined on peripheral neuroeffector systems in the pithed and in the conscious rat. 2 In the absence of a suitable means of accurately quantifying doses of inhalation anaesthetics given to small animals, an apparatus was constructed whereby end-tidal gas samples were collected semi-automatically from the mechanically ventilated rat. 3 Cyclopropane (15.3 and 29.3% end-tidal), halothane (0.20, 0.52 and 0.83% end-tidal) and diethyl ether (2% and 4% end-tidal) lowered the arterial pressure of the pithed rat. Heart rate was increased by diethyl ether 4%, decreased by halothane and unchanged by cyclopropane. 4 While each anaesthetic depressed the pressor responses to sympathetic nerve stimulation, cyclopropane increased and halothane and diethyl ether depressed the pressor responses to exogenous noradrenaline. 5 Each anaesthetic reduced the motor responses of the smooth muscle of the colon to parasympathetic stimulation. 6 The significance of the effects on peripheral neuroeffector systems is discussed in relation to the overall circulatory changes produced by these anaesthetics in the whole animal.

Animals↗
PubMed1978

An investigation of the role of ganglia in the innervation of the rat anococcygeus muscle: an electrical and mechanical study.

1 A preparation is described which allows the rat anococcygeus muscle to be stimulated via its two extrinsic nerves. Each nerve contains both excitatory and inhibitory fibres. A ganglionated nerve plexus lies on the surface of the muscle. 2 The possibility that at least part of the excitatory pathway was interrupted as a ganglion synapse lying in one of the nodes of plexus close to the muscle was suggested by the observations that (a) the excitatory response to extrinsic nerve stimulation was reduced by the nicotinic antagonists tubocurarine (0.13 to 0.26 mM) and dihydro beta-erythroidine (0.1 to 0.14 mM). (b) Fibres from one extrinsic nerve were shown to synapse on a ganglion cell from which intracellular recordings were made while the output from this ganglion cell was traced microscopically to the muscle. 3 Intracellular recording from ganglion cells in this plexus indicated that cholinergic synaptic transmission occurred in these ganglia. Tubocurarine (0.13 mM) and hexamethonium (1.3 mM) reversibly abolished intracellularly-recorded synaptic potentials. 4 Hexamethonium (0.1 to 1 mM) initially enhanced the motor response to nerve stimulation and raised muscle tone, probably by an action involving pre- and postsynaptic sites. Subsequently, hexamethonium inhibited the response to extrinsic nerve stimulation presumably by an effect at ganglia lying along the excitatory pathway. Hexamethonium enhanced, without subsequently inhibiting, the response to exogenously added noradrenaline in both untreated and 6-hydroxydopamine-treated rats. These results suggest that the initial enhancement produced by hexamethonium involved sites at postganglionic nerve endings and on smooth muscle receptors. 5 Inhibitory responses were obtained following extrinsic nerve stimulation when the tone of the muscle was raised and the excitatory response abolished by either guanethidine (3 micron) alone or by carbachol (10 micron) followed by phentolamine (3 micron). The inhibitory response was not reduced by hexamethonium (up to 2.8 mM) tubocurarine (up to 1.3 mM) or by atropine (up to 1 micron).

Action Potentials↗
PubMed1977

Effect of electrical stimulation of the autonomic nerves on the levels and synthesis of cyclic nucleotides in the rat salivary glands: relationship to enhanced growth.

Electrical stimulation of either the parasympathetic or the sympathetic nerve supply to the parotid and submaxillary glands increases the intracellular level of cyclic GMP and the rate of DNA synthesis and cell division while only sympathetic stimulation raises cyclic AMP levels. The periods of electrical stimulation inducing hyperplasia also raise the cyclic GMP concentration but there is no similar correlation with changes in cyclic AMP levels. However, the extent of hyperplasia induced by parasympathetic and sympathetic stimulation is not directly related to the size of the increase in cyclic GMP concentration that these treatments produce. Changes in cyclic AMP levels are reflected in altered in vitro adenylate cyclase activity. This activity is raised after 2 min sympathetic stimulation and markedly decreased with 30 min sympathetic or parasympathetic stimulation. Guanylate cyclase activity shows no such changes with nerve stimulation.

Adenylyl Cyclases↗
PubMed1976

The role of cyclic 3',5'-adenosine monophosphate (cyclic AMP) in the ability of sympathetic nerve stimulation to enhance growth and secretion in rat salivary glands in vivo.

1. The cyclic AMP content of the rat salivary glands was measured after sympathetic and parasympathetic nerve stimulation, and after the administration of isoprenaline and phenylephrine. 2. Stimulation of the sympathetic nerves (20 Hz, 1 msec supramaximal voltage for 30 sec of every min) initially raised the cyclic AMP level in both the parotid and submaxillary glands. The rise, which was blocked by propranolol, was not maintained and declined during stimulation from the maximum (reached after 3 min stimulation) to control levels after approximately 15 min. Stimulation of the parasympathetic nerves for 5 min did not raise the cyclic AMP levels. 3. Isoprenaline and phenylephrine raised the cyclic AMP level in both glands. 4. Theophylline enhanced the growth of the parotid and submaxillary glands as measured either by an increase in the wet and dry weights or in acinar axes lengths. N6O2-dibutyryl cyclic monophosphoric acid (dibutyryl cyclic AMP), did not enhance the growth of the glands. 5. It is concluded that cyclic AMP does not directly control cell growth in the rat salivary glands but may be a 'trigger' for events leading eventually to increased growth.

Animals↗