Effects of Ca antagonists on the action potential and their relationship to the muscarinic ACh actions in isolated sympathetic neurons of rabbits

doi:10.1016/0304-3940(86)90081-9

Neuroscience Letters

Volume 72, Issue 2, 12 December 1986, Pages 205-210

https://doi.org/10.1016/0304-3940(86)90081-9 Get rights and content

Abstract

Muscarinically induced depressions of the shoulder in the falling phase as well as the after-spike-hyperpolarization and -depolarization of the action potential in the isolated sympathetic neurons of rabbits were mimicked by a novel peptide Ca channel blocker, ω-conotoxin (synthetic; 0.1–0.5 μM). Cobalt ions (0.1–2 mM) showed bidirectional effects on the shoulder, an early depression followed by a later prolongation, while they consistently induced depressions of other components. Organic Ca channel blockers, verapamil and D-600 (1–50 μM) and nifedipine (0.1–1 μM) appeared to have other effects as they rather caused a prolongation of the falling phase that was shortened by further application of acetylcholine.

References (15)

F.J. Ehlert et al.
The binding of ³H-nitrendipine to receptor for calcium channel antagonists in the heart, cerebral cortex and ileum of rats
Life Sci.
(1982)
K. Koyano et al.
Pharmacological evidence for two types of Ca²⁺-dependent K⁺-conductance in bullfrog sympathetic ganglion cells
Neurosci. Res.
(1985)
R.J. Miller et al.
Are dihydropyridine binding sites voltage-sensitive calcium channels?
Life Sci.
(1984)
S. Mochida et al.
Activation of M₂ muscarinic receptors causes an alteration of action potentials by modulation of Ca entry in isolated sympathetic neurons of rabbits
Neurosci. Lett.
(1986)
K.M.M. Murphy et al.
Calcium antagonist receptor binding sites labelled with ³H-nitrendipine
Eur. J. Pharmacol.
(1982)
P.R. Adams et al.
Intracellular Ca²⁺ activates a fast voltage-sensitive K⁺ current in vertebrate sympathetic neurones
Nature (London)
(1982)
J.E. Freschi
Membrane currents of cultured rat sympathetic neurones under voltage clamp
J. Neurophysiol.
(1983)

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Cited by (11)

Impairment of syntaxin by botulinum neurotoxin C<inf>1</inf> or antibodies inhibits acetylcholine release but not Ca2+ channel activity
1995, Neuroscience
The involvement of syntaxin, an ω-conotoxin-sensitive Ca²⁺ channel-associated protein, in acetylcholine release was studied at synapses formed between rat sympathetic neurons in culture. Transmission at these synapses involved ω-conotoxin-sensitive Ca²⁺ channels because a dose-dependent inhibition was observed when ω-conotoxin was bath-applied. Confocal microscope examination of immunofluorescent staining showed that syntaxin had a similar distribution to synaptic vesicle-associated membrane proteins, synaptophysin and vesicle-associated membrane protein/synaptobrevin-2, indicating that syntaxin molecules are concentrated in the presynaptic terminals. Botulinum neurotoxin C₁ applied extracellularly or intracellularly into presynaptic neurons blocked synaptic transmission. Introduction of a monoclonal antibody, or polyclonal antibodies, to syntaxin into the presynaptic neuron depressed the evoked release of acetylcholine without affecting Ca²⁺ influx through Ca²⁺ channels.
These results suggest that syntaxin plays an important role in release of neurotransmitter by a nerve impulse and that this mechanism is downstream of Ca²⁺ influx.
Myosin II is involved in transmitter release at synapses formed between rat sympathetic neurons in culture
1994, Neuron
The presynaptic function of myosin II was studied at cholinergic synapses formed between rat superior cervical ganglion neurons in culture. Immunofluorescent staining showed that myosin 11 was colocalized with synaptophysin at the presynaptic nerve terminals. Antimyosin II antibody introduced into presynaptic neurons inhibited synaptic transmission. Transmission was also inhibited in a dose-dependent manner by two inhibitors of myosin light chain kinase: a peptide, SM-1, and an organic inhibitor, wortmannin. The inhibition produced by these agents was dependent on presynaptic activity. Extracellularly applied wortmannin also blocked synaptic transmission, but its effects were slower in onset. Wortmannin also decreased postsynaptic potentials and post-tetanic potentiation in intact superior cervical ganglia. These results suggest a model in which myosin light chain kinase phosphorylates myosin, and the resultant change in actin-myosin interactions is involved in neurotransmitter release.
ω-Conotoxin GVIA and Its Receptors
1992, Methods in Neurosciences
This chapter discusses ω-conotoxin and its receptors. ω-Conotoxin GVIA first described as a toxin of Conus geographus produces persistent shaking when administered intracranially to mice, but does not interact with acetylcholine receptors or voltage-sensitive sodium channels. ω-conotoxin is reported to block both N- and L-type voltage-sensitive calcium channels in nerve preparations. Recent electrophysiological reports, however, have shown that the toxin blocks only N-type channels and does not affect L-type channels in neurons. The reason for these discrepant reports can be because L-type channel action cannot be separated sufficiently in previous studies, or because the sensitivities of L-type channels to ω-conotoxin differ in different cells. There are differences in the primary structures of dihydropyridine receptors in skeletal and cardiac muscles. Therefore, the toxin blocks the L-type channels of non-neuronal tissue but does not block those in neuronal cells. The low-affinity binding site of ω-conotoxin in rat brain cannot be of L-type voltage-sensitive calcium channels or dihydropyridine binding sites, because the distributions of the two clearly differ in brain regions.
Differential blocking action of synthetic ω-conotoxin on components of Ca2+ channel current in clonal GH3 cells
1987, Neuroscience Letters
The effect of synthetic ω-conotoxin on two types of Ca²⁺ channels in clonal rat pituitary cells (GH3) was studied using the whole-cell variant of the patch-clamp technique. Low concentration of ω-conotoxin (50 nM) was sufficient to block a long-lasting Ca²⁺ channel current but a much higher concentration (1 μM) had little effect on a different type of Ca²⁺ channel current, which was activated at relatively more negative voltages and showed marked inactivation. The synthetic toxin preferentially targeted a specific type of Ca²⁺ channel and might provide a unique and powerful tool for studying the molecular properties of Ca²⁺ channels and the functional role in the process of hormonal secretion.
Live-cell imaging microscopy and quantitative analysis of Ca2+-dependent effects of neurotransmitters on DNA in snail neurons
2014, Biophysics (Russian Federation)
The synaptic vesicle glycoprotein 2A ligand levetiracetam inhibits presynaptic Ca 2+ channels through an intracellular pathway
2012, Molecular Pharmacology

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Neuroscience Letters

Abstract

References (15)

The binding of ³H-nitrendipine to receptor for calcium channel antagonists in the heart, cerebral cortex and ileum of rats

Life Sci.

Pharmacological evidence for two types of Ca²⁺-dependent K⁺-conductance in bullfrog sympathetic ganglion cells

Neurosci. Res.

Are dihydropyridine binding sites voltage-sensitive calcium channels?

Life Sci.

Activation of M₂ muscarinic receptors causes an alteration of action potentials by modulation of Ca entry in isolated sympathetic neurons of rabbits

Neurosci. Lett.

Calcium antagonist receptor binding sites labelled with ³H-nitrendipine

Eur. J. Pharmacol.

Intracellular Ca²⁺ activates a fast voltage-sensitive K⁺ current in vertebrate sympathetic neurones

Nature (London)

Membrane currents of cultured rat sympathetic neurones under voltage clamp

J. Neurophysiol.

Cited by (11)

Impairment of syntaxin by botulinum neurotoxin C<inf>1</inf> or antibodies inhibits acetylcholine release but not Ca<sup>2+</sup> channel activity

Myosin II is involved in transmitter release at synapses formed between rat sympathetic neurons in culture

ω-Conotoxin GVIA and Its Receptors

Differential blocking action of synthetic ω-conotoxin on components of Ca<sup>2+</sup> channel current in clonal GH3 cells

Live-cell imaging microscopy and quantitative analysis of Ca<sup>2+</sup>-dependent effects of neurotransmitters on DNA in snail neurons

The synaptic vesicle glycoprotein 2A ligand levetiracetam inhibits presynaptic Ca <sup>2+</sup> channels through an intracellular pathway

Effects of Ca antagonists on the action potential and their relationship to the muscarinic ACh actions in isolated sympathetic neurons of rabbits

Abstract

Life Sci.

Neurosci. Res.

Life Sci.

Neurosci. Lett.

Eur. J. Pharmacol.

Intracellular Ca2+ activates a fast voltage-sensitive K+ current in vertebrate sympathetic neurones

Nature (London)

Membrane currents of cultured rat sympathetic neurones under voltage clamp

J. Neurophysiol.

Intracellular Ca²⁺ activates a fast voltage-sensitive K⁺ current in vertebrate sympathetic neurones