Effects of activation of sodium and calcium entry on spontaneous release of acetylcholine induced by methylmercury
Atchison, W.D.
Journal of Pharmacology and Experimental Therapeutics 241(1): 131-139
1987
ISSN/ISBN: 0022-3565 PMID: 2437285 Document Number: 287989
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 .mu.M) with A23187 (25 .mu.M), a calcium ionophore, caused a more rapid time to peak induced increase in MEPP frequency that "control" MeHg preparations. This effect also occurred in solutions to which no extracellular Ca++ was added. Use of monensin, a Na+ ionophore (25-100 .mu.M), 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 .mu.M), 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. These results indicate that pathways that facilitate Ca++ entry, but not necessarily Na+ entry, can hasten the action of MeHg on spontaneous release of transmitter. Because this effect occurs in the presence of diminished extracellular Ca++, it is proposed that MeHg can gain entrance to the nerve terminal by membrane Ca++ channels.