Irreversible suppression of calcium entry into nerve terminals by methylmercury.
Measurements of uptake of 45Ca into rat forebrain synaptosomes depolarized with high K+ and EPP amplitudes at the rat neuromuscular junction were used to assess the effects of methylmercury (MeHg) on voltage-dependent Ca++ uptake and subsequent transmitter release at model central and peripheral synapses. The objectives were to: determine whether MeHg altered uptake of 45Ca into purified synaptosomes depolarized by high K+; compare its effects with those produced by HgCl2; ascertain whether the "fast" or "slow" components of Ca++ uptake were affected preferentially by MeHg; and determine whether a functional correlate to the effects on 45Ca uptake could be observed electrophysiologically at the mammalian neuromuscular junction. HgCl2 (10-500 microM) produced a concentration-dependent decrease of total depolarization-induced 45Ca uptake. Peak inhibition occurred at 200 microM Hg++ which suppressed nerve terminal Ca++ uptake to approximately 5% of Hg-free control values, a result similar to that obtained previously by others. Similarly, MeHg also suppressed total 45Ca uptake although the maximal inhibition produced (70% at 200 microM MeHg) was less than that produced by HgCl2. The effect of MeHg was apparent both in nonpreviously depolarized synaptosomes after a 1-sec depolarization ("fast uptake") and after 10-sec incubation in synaptosomes predepolarized with 41 mM K+ in Ca-free solutions before addition of MeHg and 45Ca ("slow uptake"). A significant decrease in the slow phase of 45Ca uptake occurred with 200 and 500 microM MeHg.(ABSTRACT TRUNCATED AT 250 WORDS)
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers; D066298:In Vitro Techniques; D008297:Male; D008767:Methylmercury Compounds / Q000494:pharmacology*; D009045:Motor Endplate / Q000187:drug effects; D009411:Nerve Endings / Q000187:drug effects* / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000378:metabolism
D002121:Calcium Channel Blockers; D008767:Methylmercury Compounds; D011189:Potassium Chloride; D002118:Calcium