Mechanism of inhibition of acetylcholine secretion in newly formed mouse synapses involving Ca2+-dependent kinases and voltage-gated K+-channels.
Nifedipine, a blocker of L-type Ca(2+)-channels, increased quantal content of endplate potentials in newly formed nerve-muscle synapses, while R 24571 (calmodulin inhibitor) and KN 62 (inhibitor of calmodulin-dependent kinase II) did not change it. KN 62 suppressed the increase in quantal content of endplate potentials evoked by nifedipine. Similar to nifedipine, chelerythrine and bisindolylmaleimide I (blockers of protein kinase C) increased quantal content of endplate potentials. In the presence of chelerythrine, nifedipine lost its ability to facilitate secretion of neurotransmitter. 4-Aminopyridine, a blocker of voltage-gated potassium channels, increased quantal content of endplate potentials. In the presence of chelerythrine, 4-aminopyridine induced no additional increase in the quantal content of endplate potentials. In its turn, chelerythrine induced no extra facilitation of secretion in the presence of 4-aminopyridine. It is hypothesized that Ca(2+)-dependent inhibition of secretion results from suppression of calmodulin-dependent kinase II and activation of protein kinase C, which potentiates the work of voltage-gated K(+)-channels.
Department of Human and Animal Physiology, Biological Faculty, M. V. Lomonosov Moscow State University, Russia. untergang@inbox.ru
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Bogatcheva
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Ezhova
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Balezina
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015761:4-Aminopyridine / Q000494:pharmacology; D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology; D020746:Calcium Channels, L-Type; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D051379:Mice; D018482:Muscle, Skeletal / Q000294:innervation*; D009543:Nifedipine / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013569:Synapses / Q000378:metabolism*
D053119:Benzophenanthridines; D020746:Calcium Channels, L-Type; D007093:Imidazoles; D007211:Indoles; D008301:Maleimides; D024642:Potassium Channels, Voltage-Gated; C031938:calmidazolium; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015761:4-Aminopyridine; C016299:chelerythrine; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D009543:Nifedipine; C070515:bisindolylmaleimide I; D000109:Acetylcholine