Blocking of Frog Endplate Channels by the Organic Calcium Antagonist D600

The actions of the organic ‘calcium antagonist’ D600 were examined on the frog sartorius nerve-muscle preparation. D600 blocked voltage-dependent Na+ and K+ membrane channels in nerve and muscle, and blocked also endplate channels induced by acetylcholine (ACh). The rate of spontaneous transmitter r...

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Veröffentlicht in:Proceedings of the Royal Society of London. Series B, Biological sciences Biological sciences, 1980-12, Vol.211 (1182), p.15-24
Hauptverfasser: Bregestovski, P. D., Miledi, Ricardo, Parker, Ian
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Sprache:eng
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Zusammenfassung:The actions of the organic ‘calcium antagonist’ D600 were examined on the frog sartorius nerve-muscle preparation. D600 blocked voltage-dependent Na+ and K+ membrane channels in nerve and muscle, and blocked also endplate channels induced by acetylcholine (ACh). The rate of spontaneous transmitter release from motor nerve terminals was increased by D600, independently of external Ca2+, although the drug had little effect on transmitter release evoked by nerve impulses. Postsynaptically, miniature endplate currents were reduced in size and their decay time constant became shorter and relatively independent of membrane potential. D600 reduced the increase in ACh-induced endplate current seen with membrane hyperpolarization, and with paired ACh pulses a marked depression and slow recovery of ACh sensitivity were observed. These actions of D600 on the postsynaptic membrane suggest that D600 may act by blocking open endplate channels.
ISSN:0962-8452
0080-4649
0950-1193
1471-2954
2053-9193
DOI:10.1098/rspb.1980.0155