Extracellular calcium-dependent and -independent effects of methylmercury on spontaneous and potassium-evoked release of acetylcholine at the neuromuscular junction.
Acute bath administration of methylmercury (MeHg) to the murine neuromuscular junction causes an initial surge in the frequency of occurrence of miniature end-plate potentials (MEPPs), followed by a complete suppression of asynchronous spontaneous release. The goals of the present study were to determine: whether the MeHg-induced in MEPP frequency was dependent upon extracellular Ca++, whether MeHg produced this effect by actions within the motor nerve terminal and whether the secondary suppression of release was due to transmitter depletion. Conventional intracellular microelectrode recording measurements of MEPPs were made from myofibers of the isolated hemidiaphragm of the rat. Increasing the bath concentration of Ca++ from 1 to 2 or 4 mM decreased the time period required by 100 microM MeHg to produce a peak increase of spontaneous release from 52 to 39 to 28 min, respectively. Further increasing bath Ca++ to 8 mM actually increased this period back to 49 min. Increasing [Ca++]o had no consistent effect on the magnitude of the MeHg-induced increase in MEPP frequency. After depolarization of the nerve terminal with elevated extracellular K+ (15 mM) the time to peak increases in MEPP frequency was shortened from approximately 40 min to 1 to 2 min. The time required for MeHg to cause complete cessation of MEPPs was also shortened. In experiments conducted in K+-depolarized preparations to which no Ca++ was added, MeHg still increased MEPP frequency, although not as rapidly, or to the same extent as in solutions containing Ca++.(ABSTRACT TRUNCATED AT 250 WORDS)
D000109:Acetylcholine / Q000378:metabolism*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000502:physiology*; D003035:Cobalt / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007811:Lanthanum / Q000494:pharmacology; D008297:Male; D008767:Methylmercury Compounds / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time
D008767:Methylmercury Compounds; D003035:Cobalt; D004533:Egtazic Acid; D007811:Lanthanum; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium