BAY K 8644 increases release of acetylcholine at the murine neuromuscular junction.
In this study we describe the stimulatory effects of submicromolar concentrations of BAY K 8644 on neurally evoked and spontaneous release of transmitter at the vertebrate neuromuscular junction, a model cholinergic synapse. BAY K 8644 increases mean quantal content. This effect is blocked by pretreatment with the dihydropyridine (DHP) antagonist, nimodipine, but nimodipine itself had no effect on quantal content. Furthermore, BAY K 8644 induces a marked increase in spontaneous quantal release of transmitter as measured by miniature endplate potential frequency. These results are important in that they indicate that DHP-sensitive Ca2+ channels exist at motor nerve terminals and when activated can participate in transmitter release; second, they imply that these elements do not normally participate in transmitter release; third, they indicate a functional effect of DHPs on neurons under somewhat more relevant physiological conditions than those imposed by prolonged K+-induced depolarization, a technique used to evoke transmitter release in subcellular systems and fourth, they indicate an effect of BAY K 8644 on spontaneous release of transmitter, an effect not reported in previous neurochemical experiments.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000109:Acetylcholine / Q000378:metabolism*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004095:Dihydropyridines / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009553:Nimodipine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D004095:Dihydropyridines; D007473:Ion Channels; D009553:Nimodipine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C038806:1,4-dihydropyridine; D000109:Acetylcholine