Cholinergic agonists decrease quantal output at the frog neuromuscular junction by targeting a calcium channel blocked by omega-conotoxin.
Nicotinic cholinergic agonists are known to decrease synchronous evoked quantal output at the frog neuromuscular junction [Van der Kloot 1993, J Physiol (Lond) 468:567-589]. Here we also show that carbachol decreases the frequency of miniature endplate potentials (FMEPP) in solutions containing elevated levels of K+ and Ca2+. Carbachol did not decrease FMEPP in hypertonic solutions or in solutions containing the Ca2+ ionophore ionomycin and Ca2+. We conclude that the nicotinic agonists decrease Ca2+ influx through voltage-gated Ca2+ channels. Carbachol did not alter two-pulse facilitation. A blocker of N-type Ca2+ channels, omega-conotoxin GVIA, antagonized the nicotinic agonist-induced decrease in evoked quantal output. The effect of carbachol was not altered by omega-conotoxin MVIIC, a blocker of P-type and certain other Ca2+channels. The Ca2+ channel targeted by the nicotinic agonists appears to be of the N-type.
Van der Kloot
W
W
Department of Physiology and Biophysics, SUNY at Stony Brook, Stony Brook, NY 11794-8661,USA.
Molgó
J
J
Naves
L A
LA
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000378:metabolism* / Q000502:physiology*; D018678:Cholinergic Agents / Q000494:pharmacology*; D004594:Electrophysiology; D006982:Hypertonic Solutions / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores; D009045:Motor Endplate / Q000187:drug effects / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011894:Rana pipiens; D012996:Solutions; D020866:omega-Conotoxin GVIA; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018678:Cholinergic Agents; D006982:Hypertonic Solutions; D007476:Ionophores; D010455:Peptides; D012996:Solutions; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; D015759:Ionomycin; D020866:omega-Conotoxin GVIA; D011188:Potassium