PubMed Health⌕ Search

Biomedical subjects

F R Edwards

Publications and source records attributed to F R Edwards.

At least 37 records · Page 2Linked to original sources
PubMed1994

Ionophoretically applied acetylcholine and vagal stimulation in the arrested sinus venosus of the toad, Bufo marinus.

1. The effects of acetylcholine (ACh), applied by ionophoresis, on the isolated arrested sinus venosus of the toad, Bufo marinus, were examined. 2. At each position where ACh was applied across the surface of sinus venosus preparations, a hyperpolarization was produced. These responses were abolished by hyoscine, indicating that muscarinic cholinoceptors are widely distributed over the surface of these muscle cells. 3. Vagal stimulation produced hyperpolarizations which were mimicked, to some extent, by ionophoretically applied ACh. 4. The responses to ionophoretically applied ACh were abolished by adding barium ions to the perfusion fluid, whereas responses to vagal stimulation persisted. 5. The responses to ionophoretically applied ACh were consistently slower than those to vagal stimulation. It is argued that the pathways activated by neural and applied ACh have different kinetics of activation.

Acetylcholine↗
PubMed1993

Analysis of the effects of vagal stimulation on the sinus venous of the toad.

In amphibians and mammals, vagal stimulation leads to the release of acetylcholine, ACh, which causes bradycardia. However, the responses to nerve stimulation are not well mimicked by exogenously applied ACh. These observations have led to the suggestion that there are subpopulations of muscarinic receptors on pacemaker cells and that during vagal stimulation neuronally released ACh caused slowing by suppressing inward current flow during diastole. After the generation of action potentials has been prevented by applying an organic calcium antagonist, vagal stimulation causes a hyperpolarization and an increase in membrane resistance: this observation suggests that the hyperpolarization results from a suppression of inward, presumably Na+, current flow. In this study we describe the effects of vagal stimulation on membrane potentials recorded from arrested and beating hearts by using a computer model. The model of Noble & Noble (Proc. R. Soc. Lond. B 222, 295 (1984)) was modified to describe the shape of amphibian pacemaker action potentials. A voltage-dependent Na conductance was included as well as two voltage-independent conductances, a background Na conductance and a background K conductance. Subsequently the hypothesis that the changes in membrane potential recorded during vagal stimulation from arrested preparations resulted from a reduction in Na conductance and this represented the sole action of vagally released. ACh, was tested. If this were so, the changes in membrane conductance that occur during vagal inhibitory junction potentials recorded from arrested preparations should produce changes in pacemaker action potentials similar to those recorded experimentally from beating preparations. This was found to be the case. Thus the analyses are consistent with the idea that vagal inhibition of pacemaker cells results solely from a suppression of the two pacemaker sodium currents.

Action Potentials↗
PubMed1993

Sympathetic transmission to the dilator muscle of the rat iris.

The responses of the dilator layer of the rat iris to sympathetic nerve stimulation were examined using intracellular recording techniques. Three different cell types were detected. In two of these, which were assumed to reflect recordings from myoepithelial cells, sympathetic nerve stimulation initiated excitatory junction potentials. These started after a delay of several hundred milliseconds and lasted for several seconds. The excitatory junction potentials were abolished by low concentrations of prazosin and were relatively insensitive to yohimbine, indicating that neurally released noradrenaline activated an alpha 1-adrenoceptor. The adrenoceptor was further characterised as being of the alpha 1b subtype using chlorethylclonidine. The time course of excitatory junction potentials was slowed when the preparation was cooled, suggesting that a second messenger pathway was being activated. The contractions triggered by sympathetic nerve stimulation persisted after excitatory junction potentials had been abolished by reducing the external concentration of chloride ions and after adding the organic calcium antagonist, nifedipine. Thus it seems likely that contractions of the dilator are triggered by the release of calcium ions from internal stores. These observations are discussed in relation to the idea that alpha 1b-adrenoceptors are coupled to a messenger pathway which involves inositol triphosphate and the pulsatile release of calcium ions from internal stores. The second section of the paper deals with the structure of neuro-myoepithelial contacts in the dilator layer. The majority of sympathetic varicosities formed organized neuroeffector junctions with either myoepithelial cells or melanophores. At the junctions the effector cell membrane and varicosity membrane were separated by less than 80 nm, with synaptic vesicles concentrated towards the neuroeffector junction. The synaptic vesicles in varicosities that failed to form junctions did not aggregate towards their regions of exposed membrane. These observations are discussed in relation to the idea that transmission at autonomic varicosities occurs at organised neuroeffector junctions.

Adrenergic alpha-Antagonists↗
PubMed1993

Responses to sympathetic nerve stimulation of the sinus venosus of the toad.

1. The changes in membrane potential produced by sympathetic nerve stimulation were recorded from sinus venosus preparations of the toad, Bufo marinus, in which beating had been prevented by the dihydropyridine calcium antagonist, nifedipine. 2. Supramaximal sympathetic stimuli initiated long-lasting excitatory junction potentials which started with the same latencies, some 1 to 2 s, as did sympathetic tachycardias recorded from beating preparations. 3. Brief trains of stimuli increased the amplitude of excitatory junction potentials and shortened their latency of onset. Similarly when excitatory junction potentials were facilitated their latency of onset was shortened. 4. The time courses of excitatory junction potentials were prolonged by cooling the preparation but unchanged when the neuronal uptake of catecholamines was inhibited. 5. In arrested preparations, beta-adrenoceptor activation causes a hyperpolarization, as did the inhibition of phosphodiesterases or the activation of adenylate cyclase. This contrasts with the depolarization produced by sympathetic nerve stimulation which could be mimicked by the rapid application of either adrenaline or noradrenaline but not by beta-adrenoceptor activation, phosphodiesterase inhibition or by adenylate cyclase activation. 6. The results are discussed in relation to the idea that neuronally released adrenaline activates a set of adrenoceptors which are linked to a set of channels by a pathway that does not involve cyclic AMP.

Amines↗
PubMed1993

Cholinergic neuromuscular transmission in the longitudinal muscle of the guinea-pig ileum.

1. Brief transmural stimuli, 0.5-1 ms, initiated contractions of the longitudinal muscle taken from the guinea-pig ileum that were recorded isometrically. In separate preparations similar stimuli were found to initiate excitatory junction potentials which were recorded using intracellular recording electrodes. All of these responses were abolished by either tetrodotoxin, omega-conotoxin or hyoscine. 2. The contractions produced by increasing [K+]o were blocked by nifedipine, 1 x 10(-7) M; nicardipine, 1 x 10(-7) M; verapamil, 1 x 10(-5) M or diltiazem, 1 x 10(-5) M. In these solutions brief stimuli continued to initiate contractions: this indicates that neuronally released acetylcholine continues to trigger a contraction when muscle voltage-dependent calcium channels appear to have been blocked. 3. When membrane potential recordings were made from the smooth muscle layer, brief transmural stimuli initiated excitatory junction potentials that triggered muscle action potentials. Although muscle action potentials were abolished by low concentrations of a range of organic calcium antagonists, excitatory junction potentials persisted and continued to initiate contractions of reduced amplitude. 4. When the internal concentration of calcium ions, [Ca2+]i, was measured using fura-2, brief transmural stimuli caused an increase in [Ca2+]i. Part of this response, which occurred at a time corresponding to the unblocked excitatory junction potential, persisted in the presence of the organic calcium antagonist nifedipine. 5. Two explanations appear possible. Neuronally released acetylcholine may simultaneously activate non-selective cation channels and cause the release of Ca2+ from an internal store. Alternatively, neuronally released acetylcholine may cause an increase in [Ca2+]i which is separate from that which accompanies the activation of voltage-dependent calcium channels. At this stage there is little other anatomical or electrophysiological evidence to support this view.

Action Potentials↗
PubMed1993

Effects of sympathetic nerve stimulation on the sino-atrial node of the guinea-pig.

1. The effects of sympathetic nerve stimulation on the generation of pacemaker action potentials, recorded from the sino-atrial node of the guinea-pig, were determined by using intracellular recording techniques. 2. Trains of stimuli applied to the right stellate ganglion led to an increase in heart rate after a delay of a few seconds. During the initial phase of the tachycardia the rate of discharge of pacemaker action potentials increased and the rate of diastolic depolarization increased, but both the peak diastolic potential and the maximum rate of rise of the action potentials were reduced. During the later phase of the tachycardia the peak diastolic potential, the amplitude of the action potentials, the maximum rate of rise and the rate of repolarization of the action potentials were increased. 3. When membrane potential recordings were made from sino-atrial node cells, in which beating had been abolished by adding the organic calcium antagonist nifedipine, sympathetic nerve stimulation initiated excitatory junction potentials (EJPs) which had time courses similar to those of the tachycardias recorded from beating preparations. 4. Although both the tachycardias produced by either sympathetic nerve stimulation or added noradrenaline were largely abolished by beta-adrenoceptor antagonists, the membrane potential changes recorded during the responses to sympathetic nerve stimulation or added noradrenaline were different. Bath-applied noradrenaline caused a tachycardia which was associated with an increase in the amplitudes of pacemaker action potentials, an increase in the peak diastolic potential and a shortening in the duration of pacemaker action potentials. 5. The addition of agents which cause the accumulation of cyclic AMP in the cytoplasm of the cells produced a tachycardia which was associated with a similar sequence of changes in the membrane potentials to those produced by added noradrenaline; again the membrane potential changes produced by these agents differed from those produced by sympathetic nerve stimulation. 6. The results are discussed in relation to the idea that neurally released noradrenaline activates a set of receptors which cause tachycardia by increasing inward current flow during diastole, whereas added noradrenaline activates a set of receptors that are linked to a cyclic AMP-dependent pathway which modifies the properties of some of the voltage-dependent channels involved in pacemaking activity.

Action Potentials↗
PubMed1992

Transmission at autonomic neuroeffector junctions.

For organs innervated by the autonomic nervous system, it is generally held that neuroeffector transmission is achieved by varicosities releasing transmitters some distance from the membranes of target cells. Transmitters are thought to diffuse through the extracellular space and interact with post-junctional receptors that are widely distributed over the cell membranes. This article presents an alternative view, suggesting that transmission can occur at organized neuroeffector contacts, that transmitters interact with restricted pools of specialized junctional receptors, and that many receptors on target cells are not involved in neuroeffector transmission.

Animals↗
PubMed1992

Neural and metabolic control of arteriolar diameter.

During sympathetic nerve activity, sympathetic transmitter causes depolarizations which trigger voltage dependent Ca++ entry. The ability of arteriolar membranes to sum together successive e.j.ps is changed as a consequence of cellular activity, i.e. increased [K+]o. Furthermore, the ability of arteriolar membrane to permit voltage dependent Ca++ entry is modified by a second consequence of cellular activity, i.e. changes in external pH.

Animals↗
PubMed1991

Development of a functional innervation of the iris dilator muscle by sympathetic nerve fibres in the rat.

These studies using both in situ and in vitro preparations were designed to determine the time of onset of a functional sympathetic innervation to the dilator muscle of the rat iris during postnatal development. The preganglionic nerve trunk to the superior cervical ganglion was stimulated and measurements made of pupil diameter. Alternatively, intracellular recordings were made from the dilator muscle cells and the response to stimulation of the intramural nerves was measured. During the second postnatal week, a decrease in the resting pupil diameter under low lighting conditions was observed, reflecting the normal developmental increase in size of the iris. On account of the small size of the iris in rats up to 10 days postnatal, the in vivo experiments were a reliable test of a functional innervation only in older animals. In all cases, stimulation of the preganglionic nerve trunk in situ caused dilatation of the pupil. Stimulation of the sympathetic nerves in vitro, in preparations of iris taken from rats of various ages, evoked a slow depolarisation mediated via alpha adrenoceptors. Such responses could be recorded in irides from rats as young as 3 days postnatal. Spontaneous activity was recorded in irides towards the end of the second postnatal week just prior to the time of normal eye opening, and may reflect the onset of photomechanical coupling. We conclude that the sympathetic nerves within the iris are capable of evoking membrane potential changes in the dilator muscle cells in the early postnatal period, well before the nerve plexus in the iris is fully differentiated.

Animals↗
PubMed1990

Effects of vagal stimulation and applied acetylcholine on the arrested sinus venosus of the toad.

1. The effects of vagal stimulation and applied acetylcholine were compared on sinus venosus preparations of the toad, Bufo marinus, in which beating had been inhibited by adding the organic calcium antagonist nifedipine. 2. Bath-applied acetylcholine and vagal stimulation each caused membrane hyperpolarizations which were abolished by hyoscine. 3. Whereas the hyperpolarization that accompanied vagal stimulation was largely unaffected by barium ions, that produced by bath-applied acetylcholine was almost abolished. 4. Caesium ions also prevented the hyperpolarization produced by bath-applied acetylcholine but potentiated the responses to vagal stimulation. 5. The membrane resistance of arrested sinus venosus cells was found to be higher during vagal stimulation than in the absence of stimulation. In contrast when a similar hyperpolarization was produced by adding acetylcholine, the membrane resistance was found to be lower than in control solution. 6. The results are discussed in relation to the idea that neuronally released acetylcholine causes membrane hyperpolarization by suppressing inward current flow and applied acetylcholine acts to increase outward current flow.

Acetylcholine↗
PubMed1990

Sympathetic nerve stimulation and applied transmitters on the sinus venosus of the toad.

1. The effect of sympathetic nerve stimulation on pacemaker cells of the isolated sinus venosus of the toad, Bufo marinus, were examined using intracellular recording techniques. 2. Train of stimuli applied to the sympathetic outflow led to a two-component increase in heart rate. Shortly after the onset of stimulation the rate of discharge of pacemaker action potentials increased. After the end of the train of stimuli, the heart rate fell and then again increased to remain high for several minutes. 3. During the early tachycardia, the peak diastolic potential was reduced and the rate of diastolic depolarization increased. During the late tachycardia, the peak diastolic potential and rate of diastolic depolarization were increased; both the amplitude and the rate of repolarization of the action potentials were increased. 4. When membrane potential recordings were made from sinus venosus cells in which beating had been abolished by adding the organic calcium antagonist nicardipine, sympathetic nerve stimulation caused membrane depolarization. 5. The responses to sympathetic nerve stimulation, recorded from beating or arrested hearts, were abolished by bretylium but persisted in the presence of a number of beta-adrenoceptor antagonists. 6. Bath-applied adrenaline caused a tachycardia which was associated with a large increase in the amplitudes of pacemaker action potentials. These effects were largely mediated by the activation of beta 2-adrenoceptors. 7. In the presence of high concentrations of beta-adrenoceptor antagonists, applied adrenaline produced membrane potential changes that although slower in time course were similar to those produced by sympathetic nerve stimulation. 8. Many aspects of the responses to nerve stimulation could be mimicked by applied ATP. 9. The early phase of sympathetic tachycardia was abolished after P2-purinoceptor desensitization; this phase was also inhibited by dihydroergotamine. 10. The results are discussed in relation to the idea that sympathetic nerve stimulation causes the early tachycardia by increasing inward current flow during diastole, a response involving activation of specialized adrenoceptors and perhaps ATP receptors.

Action Potentials↗
PubMed1989

Noradrenaline (gamma) and ATP responses of innervated and non-innervated rat cerebral arteries.

1. The distribution of sympathetic adrenergic nerves on the rat middle cerebral artery and on the arterioles which originated from it was determined by use of gloxylic histochemistry. 2. Whereas the middle cerebral artery and proximal arterioles arising from this artery received a sympathetic innervation, the distal regions of the same arterioles were devoid of innervation. 3. The arteries and arterioles which were innervated were depolarized by noradrenaline in the combined presence of alpha- and beta-adrenoceptor antagonists. Those which were not innervated were not depolarized by noradrenaline. 4. ATP depolarized all arteries and arterioles examined. 5. These observations are discussed with respect to the similarities and differences between gamma-adrenoceptors and P2 purinoceptors.

Adenosine Triphosphate↗
PubMed1989

The effects of vagal stimulation and applied acetylcholine on the sinus venosus of the toad.

1. The effects of vagal stimulation and applied acetylcholine were compared on the isolated sinus venosus preparation of the toad, Bufo marinus. 2. The effects of applied acetylcholine and of low-frequency, or short bursts of high-frequency vagal stimulation were abolished by hyoscine. 3. When intracellular recordings were made from muscle cells of the sinus venosus, it was found that applied acetylcholine caused bradycardia and a cessation of the heart beat which was associated with membrane hyperpolarization and a reduction in the duration of the action potentials. Much of the effect of acetylcholine can be attributed to it causing an increase in potassium conductance, gK. 4. When slowing was produced by low-frequency vagal stimulation, only a small increase in maximum diastolic potential was detected. During vagal arrest the membrane potential settled to a potential positive of the control maximum diastolic potential. 5. In the presence of barium, much of the bradycardia associated with vagal stimulation persisted. Although the bradycardia produced by added acetylcholine also persisted in the presence of barium, the effects of acetylcholine that could be attributed to an increase in gK were abolished. 6. Addition of caesium ions produced bradycardia with membrane potential changes similar to those seen during vagal stimulation. 7. The results are discussed in relation to the idea that neuronally released acetylcholine reduces inward current flow during diastole. In contrast applied acetylcholine as well as reducing inward current flow during diastole also increases outward current flow by increasing gK.

Acetylcholine↗
PubMed1989

Effects of vagal stimulation and applied acetylcholine on pacemaker potentials in the guinea-pig heart.

1. Intracellular recordings were made from pacemaker cells lying in the sino-atrial node of guinea-pigs. 2. Low-frequency vagal stimulation slowed the rate of generation of pacemaker action potentials; high-frequency stimulation stopped the generation of action potentials. 3. During vagal stimulation the rate of diastolic depolarization was reduced with the action potential otherwise unchanged: when the heart stopped the membrane potential of pacemaker cells settled to a value positive of the maximum diastolic potential. 4. In contrast, added acetylcholine caused membrane hyperpolarization and shortened the duration of action potentials. 5. The effects of both added acetylcholine and vagally released acetylcholine were abolished by hyoscine. 6. It is suggested that neurally released acetylcholine acts to change the balance between inward and outward current flow during diastole by modifying the properties of existing voltage-dependent channels. In contrast added acetylcholine appears to activate a different set of receptors which increase the potassium conductance of pacemaker cells.

Acetylcholine↗
PubMed1989

Reduction by baclofen of monosynaptic EPSPs in lumbosacral motoneurones of the anaesthetized cat.

1. Monosynaptic excitatory postsynaptic potentials (EPSPs) were elicited in lumbosacral motoneurones of pentobarbitone anaesthetized cats by stimulating group Ia muscle afferents with most of the dorsal roots severed. In some experiments Ia EPSPs were recorded together with monosynaptic EPSPs elicited by stimulating the ipsilateral ventral quadrants (VQ) of the thoracic spinal cord. Injection of (+/-) baclofen (1 mg kg-1 I.V.) caused a reduction in the peak amplitudes of both Ia and VQ EPSPs, which started immediately upon injection and progressed gradually. No recovery in EPSP amplitude was seen during the recording period, which lasted up to 60 min. 2. The Ia EPSP peak amplitude was reduced by 18-61% (mean +/- S.D., 38 +/- 14%; n = 30), while VQ EPSPs were reduced by 7-42% (23 +/- 13%; n = 5). Baclofen had a significantly larger effect on Ia EPSPs than VQ EPSPs (P less than 0.001; t test). 3. Baclofen did not cause any consistent change in the membrane potential, nor in the membrane time constant, as estimated from the exponential decay of the tail of the EPSP. There was no tendency for the reduction in peak EPSP amplitude to be related to the estimated electrical distance on the dendritic tree at which the synaptic current was injected. 4. For two I a and two VQ EPSPs, the trial-to-trial fluctuation in the peak amplitude was resolved into quantal parameters before and after baclofen was administered. The reduction in peak amplitude was in all cases accounted for by a reduction in the probability of release of neurotransmitter, with no change in quantal size. Other EPSPs either showed negligible trial-to-trial amplitude fluctuation, or could not be resolved into quantal parameters without ambiguity. 5. By comparing the variance components of the EPSP peak amplitude distribution, the hypothesis was tested that the entire action of baclofen was to reduce quantal amplitude. This was rejected for sixteen out of thirty Ia and three out of five VQ EPSPs (P less than 0.05). 6. These results support a presynaptic site of action of baclofen on the terminals of Ia afferents, by decreasing the probability of release of neurotransmitter. They also indicate a similar, although weaker, action on VQ terminals. No evidence was found for an action on the postsynaptic membrane properties or synaptic conductance.

Animals↗
PubMed1988

Inward rectification in submucosal arterioles of guinea-pig ileum.

1. The current-voltage relationships of short segments of submucosal arteriole of guinea-pig have been determined using constant current and voltage clamp techniques. 2. The current-voltage relationships were non-linear over the membrane potential range -60 to -90 mV, the conductance increasing with hyperpolarization. 3. The membrane potential ranges over which the membrane conductance increased were changed by changing the external concentration of potassium ions. 4. Changing the external concentrations of sodium and chloride ions had no effect on the arteriolar current-voltage relationships. 5. The hyperpolarization-activated conductance increase was prevented by low concentrations of barium ions. 6. It is suggested that these arterioles display potassium-selective inward rectification and that the rectifier supplies the dominant resting potassium conductance. The properties of this rectifier are compared with those of other tissues.

Action Potentials↗
PubMed1988

Inward rectification in rat cerebral arterioles; involvement of potassium ions in autoregulation.

1. The resting membrane potentials of proximal and distal segments of the arterioles which arise from the rat middle cerebral artery were determined. Proximal segments had stable membrane potentials with a mean value of -69 mV. The membrane potentials of distal segments were less negative and often unstable. 2. When the extracellular concentration of potassium ions [( K+]o) was increased proximal segments of arteriole were depolarized whereas distal ones were hyperpolarized. When [K+]o was decreased both proximal and distal segments were depolarized, the changes being more marked in proximal arterioles. 3. The membranes of proximal segments of arteriole displayed inward rectification at potentials near rest; inward rectification in distal segments of arteriole, when detected, was less pronounced. 4. The activation curve for inward rectification in proximal segments of arteriole was changed by changing the extracellular concentration of K+. A reduction in [K+]o caused the activation curve to move to such negative potentials that the inward rectifier no longer contributed to the resting conductance. 5. Increasing [K+]o changed the activation curve for inward rectification in distal segments of arteriole so that more K+ current flowed at potentials near resting. At the same time the membrane potential hyperpolarized. 6. The results are discussed in relation to autoregulatory changes which occur following changes in the K+ concentration of cerebrospinal fluid.

Animals↗