Effects of activation of sodium and calcium entry on spontaneous release of acetylcholine induced by methylmercury.
The effect of ionophores and channel activators for Ca and Na on the time course and magnitude of methylmercury (MeHg)-induced increase in spontaneous release of neurotransmitter was studied at the murine neuromuscular junction using intracellular microelectrode recording techniques. The goal was to test whether chemicals that increase entry of Na+ or Ca++ into nerve terminals would shorten the latent period that precedes the onset of MeHg-induced increase in MEPP frequency. Administration of MeHg (100 microM) with A23187 (25 microM), a calcium ionophore, caused a more rapid time to peak induced increase in MEPP frequency than "control" MeHg preparations. This effect also occurred in solutions to which no extracellular Ca++ was added. Use of monensin, a Na+ ionophore (25-100 microM), did not shorten the time to peak increase of MEPP frequency. The dihydropyridine Ca++ channel agonist Bay K 8644 (750 nM) produced the most marked shortening of the time to peak MEPP frequency for MeHg. This effect also occurred in solutions deficient in extracellular Ca++. Veratridine (20 microM), a sodium channel activator, decreased the time to peak MEPP frequency when used in conjunction with MeHg in both Ca++-containing and Ca++-deficient solutions. Replacement of sodium in the extracellular perfusion solution with methylamine, which does not penetrate axon sodium channels, did not prevent the MeHg-induced increase in MEPP frequency although it did prolong the time to peak increase and decreased the maximal MEPP frequency induced by MeHg compared with experiments conducted in sodium-containing solutions.(ABSTRACT TRUNCATED AT 250 WORDS)
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D005071:Evoked Potentials / Q000187:drug effects; D008297:Male; D008767:Methylmercury Compounds / Q000494:pharmacology*; D008839:Microelectrodes; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism*; D013997:Time Factors; D014701:Veratridine / Q000494:pharmacology
D008767:Methylmercury Compounds; D000001:Calcimycin; D014701:Veratridine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D012964:Sodium; D000109:Acetylcholine; D002118:Calcium