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E M Silinsky

Publications and source records attributed to E M Silinsky.

53 records · Page 3Linked to original sources
PubMed1980

Evidence for specific adenosine receptors at cholinergic nerve endings.

1 An electrophysiological study was made to determine if adenosine and adenine nucleotides affect cholinergic nerve endings to frog skeletal muscle through relatively non-specific nucleotide receptors or through specific adenosine receptors. 2 Non-hydrolysable derivatives of adenosine triphosphate failed to alter the mean number of acetylcholine (ACh) quanta released by the nerve impulse (m) or the miniature endplate potential frequency (m.e.p.p.f) but N6-methyladenosine and 2-chloroadenosine, two adenosine analogues with an unsubstituted ribose moiety (R-site agonists), produced marked reductions in m and m.e.p.p.f. 3 In contrast, 2'-deoxyadenosine, a derivative with an unsubstituted purine ring (P-site agonist), generally produced increases in m and m.e.p.p.f, which further increased after removing the drug. Other P-site agonists such as 5'-deoxyadenosine (in the presence of theophylline) and 9-beta-D-arabinofuranosyl adenine also increased m and m.e.p.p.f. 4 The results suggest that two types of adenosine receptors may be present at cholinergic nerve endings, one type (R-site) mediating depression and the other type (P-site) producing enhancement of ACh release.

Acetylcholine↗
PubMed1978

Enhancement by an antagonist of transmitter release from frog motor nerve terminals.

1 The effect of Ba2+ on the synchronous release of acetylcholine from frog motor nerve terminals was studied by conventional electrophysiological techniques. 2 When Ca2+ and Ba2+ were the only divalent cations in the bathing fluid, Ba2+ caused a presynaptic reduction in the amplitude of the endplate potential (e.p.p.). This effect was surmountable by increasing the Ca2+ concentration. 3 The affinity constant (KA) for Ba2+, calculated on the assumption that Ba2+ is a competitive inhibitor of the agonist, Ca2+, was 1.1 +/- 0.4 mM-1 (mean +/- s.e. mean, n = 8). 4 When e.p.ps were depressed by the addition of 1 mM Mg2+, addition of Ba2+ (1 to 3 mM) caused either a further presynaptic depression of moderate magnitude or had no additional effect. 5 When e.p.p.s were depressed with [Mg2+] greater than or equal to 2 mM, addition of Ba2+ greater than or equal to 0.9 mM enhanced the e.p.p. amplitude by a presynaptic mechanism. 6 The interaction of the divalent cation antagonists Mg2+ and Ba2+ with the agonist, Ca2+ is discussed. It is demonstrated that a model which considers the nonequilibrium, kinetic properties of binding can be used to describe interactions between divalent cations at the external surface of the motor nerve ending.

Acetylcholine↗
PubMed1978

On the conductance pathway traversed by strontium in mediating the asynchronous release of acetylcholine by motor nerve impulses.

A study was made to determine whether the Sr2+ dependent asynchronous release of acetylcholine by nerve impulses is mediated by the conventional Ca2+ conductance channel or, as has been suggested recently, through an alternative ion pathway. Experiments were performed on the frog neuromuscular junction by the use of standard electrophysiological techniques. Repetitive nerve stimulation in Sr2+-Ringer solutions caused a marked increase in miniature end-plate potential (m.e.p.p.) frequency which was dependent on Sr2+ concentration and inhibited in a competitive fashion by the known Ca2+ antagonists, Co2+ and Mg2+. The equilibrium dissociation constants (KdS) determined for both Co2+ (0.09 +/- 0.01 mM, mean +/- s.e. mean, n = 5) and Mg2+ (3.7 +/- 0.3 mM, mean +/- s.e. mean, n = 4) were essentially the same as the reported values for these antagonists in blocking Ca2+ -mediated transmitter release by nerve impulses. These results suggest that Sr2+ mediates asynchronous evoked transmitter release through the conventional calcium conductance channel.

Acetylcholine↗
PubMed1978

On the role of barium in supporting the asynchronous release of acetylcholine quanta by motor nerve impulses.

1. The effect of Ba2+ on the evoked secretion of individual acetylcholine (ACh) quanta was studied on frog neuromuscular junctions using conventional electro-physiological techniques. 2. In solutions containing 1.8 mM-Ba2+ and no added Ca2+, 1 Hz stimulation for less than 1 min elevated miniature end-plate potential (m.e.p.p.) frequencies to 5-20 times the control level (seven experiments). Similar results were obtained when a Ca2+-chelating agent was added to the Ba2+ solution. 3. Repetitive nerve stimulation at frequencies greater than 1 Hz in concentrations of Ba2+ greater than or equal to 1.8 mM elevated m.e.p.p. frequencies to unmeasurable levels (greater than 100/sec). Such high m.e.p.p. frequencies were accompanied by a steady depolarization of the post-synaptic membrane, which was used to estimate the number of ACh quanta released. 4. The number of ACh quanta released asynchronously by nerve impulses was directly related to the external concentration of Ba2+ in a non-linear fashion. 5. Ba2+ was two orders of magnitude more effective than Ca2+ in supporting the evoked discharge of m.e.p.p.s. Ca2+ was a potent antagonist of asynchronous release in Ba2+ solutions. 6. Mg2+ and Co2+ both competitively antagonized evoked release in Ba2+ solutions. The equilibrium dissociation constant for each ion as an antagonist of asynchronous, Ba2+-dependent release was similar to its corresponding value as an antagonist of synchronous, Ca2+-mediated release. 7. It is suggested that Ba2+ supports dispersed, quantal ACh release directly by acting through the same conductance pathway normally traversed by Ca2+.

Acetylcholine↗
PubMed1977

Can barium support the release of acetylcholine by nerve impulses?

Conventional electrophysiological techniques were used to study the effects of Ba on the release of acetylcholine (ACh) from frog motor nerve terminals. Equimolar substitution of Ba for Ca eliminated end-plate potentials (e.p.ps) without a corresponding decline in the amplitude of the nerve terminal action potential. Miniature end-plate potentials (m.e.p.ps) were readily detectable in Ba solutions despite a depolarized muscle membrane. Studies on the e.p.p. in curarized preparations bathed with different concentrations of Ca and Ba suggest that Ba may compete with Ca in the process by which depolarization of the nerve terminal leads to the release of ACh. Repetitive nerve stimulation at 1 Hz in Ba solutions caused 5-20 fold increases in m.e.p.p. frequencies (7 experiments). Stimulation of Ba-bathed preparations at 10 Hz elevated m.e.p.p. frequencies to very high levels that could not be measured accurately (''100/s). It is suggested that the asynchronous discharge of m.e.p.ps produced by repetitive nerve stimulation is the electrophysiological correlate of the evoked ACh outflow in Ba solutions detected previously by bioassay of ther perfusion fluid.

Acetylcholine↗
PubMed1977

An estimate of the equilibrium dissociation constant for calcium as an antagonist of evoked acetylcholine release: implications for excitation-secretion coupling.

The equilibrium dissociation constant (K(d)) for Ca(2+) as an antagonist of evoked acetylcholine (ACh) release was determined in the hope of distinguishing whether divalent cations control excitation-secretion coupling selectively (by binding with high affinity to an external membrane site) or non-selectively (by screening fixed negative charges on the external surface of the nerve terminal). ACh release was detected electrophysiologically by means of conventional intracellular recording techniques at frog motor endplates. Ba(2+) was used as the agonist to support the asynchronous release of ACh by repetitive motor nerve impulses. Despite its dispersed nature, release mediated by Ba(2+) occurs through the same conductance pathway as synchronous release mediated by Ca(2+). Ca(2+) was found to be a potent antagonist of Ba(2+)-dependent release with a K(d)=0.12+/-0.02 mM (mean+/-s.e. mean, n=5). This value is 30-50 times lower than the K(d) for Mg(2+) as an antagonist of the same release process. It is suggested that antagonism of release by Ca(2+) is likely to be exerted at the same external site that binds other divalent cation antagonists, a site that appears essential for the agonist behaviour of Ca(2+). The high affinity (low K(d)) of Ca(2+) as an antagonist of ACh release suggests that a selective, binding model appears to be the most appropriate single description of the action of divalent cations at the external surface of the motor nerve ending.

Acetylcholine↗
PubMed1976

Interaction between inhibitory and excitatory synaptic potentials at a peripheral neurone.

1. The interaction between inhibitory and excitatory synaptic potentials in neurones lying in the submucous plexus of guinea-pig ileum has been examined. 2. It was found that during an inhibitory conductance change, electrotonic potentials were more depressed in amplitude than were excitatory synaptic potentials. 3. It is suggested that inhibitory conductance changes may have only a slight effect on the impedance seen by excitatory synaptic currents as much of the excitatory synaptic current flow is likely to be capacitive. 4. A part of the depression of excitatory synaptic potential amplitude was not associated with changes in electrical properties of neurones and it is suggested that inhibitory transmitter may reduce the release of excitatory transmitter.

Action Potentials↗
PubMed1976

On the receptors which mediate the hyperpolarization of salivary gland cells of Nauphoeta cinerea Olivier.

The actions of sympathomimetics and of catecholamine antagonists have been investigated on the membrane potential and responses to nerve stimulation of acinar cells of the salivary gland of Nauphoeta cinerea Olivier. 2. Hyperpolarizations such as those evoked by nerve stimulation and by low concentrations of adrenaline, noradrenaline and dopamine were not produced by the alpha-agonists amidephrine and methoxamine. Isoprenaline was active, but only in concentrations above 100 muM. 3. Tyramine, an indirectly acting sympathomimetic, and high concentrations of methoxamine caused an increase in the rate of the small transient hyperpolarizations sometimes seen in the absence of stimulation. 4. The response to nerve stimulation was unaffected by propranolol (20 muM) an alpha-adrenergic antagonist. Phentolamine, an alpha-adrenergic antagonist, reduced matching responses to nerve stimulation and to dopamine to about the same extent. 5. As on other systems responsive to low concentrations of dopamine, apomorphine was active, although only in high concentration, and ergometrine and methysergide were antagonistic both to nerve stimulation and to dopamine.

Adrenergic alpha-Agonists↗
PubMed1975

On the association between transmitter secretion and the release of adenine nucleotides from mammalian motor nerve terminals.

1. Conventional electrophysiological techniques were used to record from isolated rat phrenic nerve-hemidiaphragm preparations. After periods of rest (20 min) or nerve stimulation (7/sec for 20 min) the bathing medium of the preparation was removed and assayed for adenosine triphosphate (ATP) and adenosine diphosphate (ADP) using a sensitive modification of the firefly luciferase method (Silinsky, 1974). 2. In the presence of tubocurarine and normal (2 mM) calcium, fourteen periods of nerve stimulation (eight preparations) caused the appearance of ATP and/or ADP in amounts ranging from 28 to 641 p-mole. Experiments using carbachol (30 muM or 1 mM) suggested that this nucleotide efflux was not produced by a secondary action of released acetylcholine (ACh). 3. Stimulation of isolate phrenic nerve trunks at 7/sec for 20 min did not cause the efflux of ATP or ADP. 4. In solutions of normal osmotic pressure and reduced calcium concentrations (0-1 mM or 'calcium-free'), stimulation failed to release adenine nucleotide from non-contracting preparations. 5. Diaphragms were bathed in normal calcium and indirectly stimulated at 11/sec for 80-90 min in the presence of 5 times 10-minus 5 M hemicholinium-3. After all detectable signs of ACh release were eliminated, nerve stimulation failed to release ATP or ADP. 6. These results in conjunction with experiments on the hydrolysis of exogenous ATP suggest that ATP is released from the motor nerve ending and is subsequently degraded by enzymatic activity. It is also suggested that the released nucleotide may be derived from the cholinergic vesicle.

Acetylcholine↗
PubMed1975

Some effects of 5-hydroxytryptamine, dopamine and noradrenaline on neurones in the submucous plexus of guinea-pig small intestine.

1. Responses to the iontophoretic application of 5-hydroxytryptamine (5-HT), dopamine and noradrenaline were examined in neurones of the submucous plexus of guinea-pig small intestine. 2. Every neurone was excited by 5-HT. 3. In a proportion of cells, dopamine or noradrenaline caused an increase in membrane potential. This response was only observed in cells which received in inhibitory innervation. The responses closely resembled inhibitory synaptic potentials evoked by transmural stimulation. 4. Both inhibitory synaptic potentials and inhibitory responses to dopamine and noradrenaline were blocked by methysergide. 5. It seems possible that these two catecholamines may interact with similar receptors to those activated by inhibitory transmitter.

Animals↗
PubMed1974

The effects of bretylium and guanethidine on catecholaminergic transmission in an invertebrate.

1 Secretory potentials produced by stimulation of the salivary duct nerves were recorded intracellularly from cockroach isolated salivary glands. The secretory potential normally consisted of a 40-80 mV hyperpolarization of the gland cell.2 Bretylium (0.1-1 mM) reduced the amplitude of the secretory potential without affecting the response of the gland to dopamine (0.25-1 muM). In addition, bretylium caused an increase in the frequency of miniature secretory potentials and the appearance of nerve terminal action potentials.3 Guanethidine (1 mM) reduced the response to nerve stimulation without depressing the sensitivity of the salivary gland to dopamine (0.25-0.5 muM) and without causing an increase in the occurrence of miniature potentials. Higher concentrations (4-5 mM) completely eliminated secretory potentials but also reduced the sensitivity of the gland cell to dopamine.5 These results indicate a presynaptic depression of the secretory potential by both bretylium and guanethidine. It is suggested that, in this system, bretylium acts by depolarizing the nerve terminal while guanethidine does not.

Action Potentials↗
PubMed1974

Conductance changes associated with the secretory potential in the cockroach salivary gland.

1. Conductance changes in the acini of the cockroach salivary gland have been examined during nerve stimulation by means of two intracellular electrodes placed in the same acinus, the first electrode being used for recording membrane potential and the second for current injection.2. The transient hyperpolarization (secretory potential) in the acinus evoked by nerve stimuli is accompanied by a rise in membrane conductance. The conductance, however, remains high for a longer period than that of the response.3. Applying the analysis of Trautwein & Dudel (1958) to the secretory potentials recorded in the acinus (assumed to behave electrically like a single cell) gives estimates of the ;transmitter equilibrium potential'. The values indicate that the neurotransmitter increases the membrane potassium conductance.4. The hyperpolarization of the acinus evoked by 10(-6)M dopamine in the bathing fluid is also associated with an increase in membrane potassium conductance.

Animals↗
PubMedDate not supplied

Inhibition of acetylcholine release from preganglionic frog nerves by ATP but not adenosine.

ATP is known to be released in association with acetylcholine at synapses in the vertebrate peripheral nervous system. Exogenously applied ATP and its derivatives have been shown to reduce the release of acetylcholine, so it has been postulated that ATP has a role in the modulation of transmitter secretion. More recent results have suggested, however, that specific adenosine receptors are responsible for the inhibitory effects of adenosine derivatives on transmitter release, and ATP, if released, must be hydrolysed to adenosine to produce inhibition. The original hypothesis that ATP itself might inhibit acetylcholine secretion would be strengthened if it were found that adenosine is very much less potent than ATP as an inhibitor of ACh secretion. We report here results which show this is the case in sympathetic ganglia.

Acetylcholine↗