Abstract:
:Methylmercury (MeHg) causes a multiphasic disruption of intraneuronal cation regulation. Release of Ca2+ from internal stores and entry of extracellular Ca2+ (Ca2+e) contribute to the temporally distinct early (first Ca2+ phase) and late (second Ca2+ phase) components of increased intracellular Ca2+ concentration ([Ca2+]i). The present study was designed to explore the mechanisms mediating the second Ca2+ phase. Fluorescence intensity was monitored from single NG108-15 cells loaded with fura-2 before and during acute application of 2 microM MeHg. Nifedipine (1 or 10 microM but not 0.1 microM) significantly delayed the time-to-onset of the second Ca2+ phase. Nifedipine (1 microM but not 0.1 microM) also caused a concentration-dependent delay in the onset of both the first Ca2+ phase which is independent of Ca2+e and the elevation of non-Ca2+ cation (non-Ca2+ phase). The L-type dihydropyridine (DHP) Ca2+ channel agonist Bay K-8644 (10 nM) had no effect on the time-to-onset of the second Ca2+ phase. Neither the N-type Ca2+ channel blocker omega-conotoxin GVIA (up to 1 microM) nor the nonselective Ca2+ channel blocker Ni2+ (1 mM) altered the time-to-onset of the second Ca2+ phase. Removal of Na+e or addition of the voltage-dependent Na+ channel antagonist tetrodotoxin (TTX, 1 microM) significantly delayed the onset of the second Ca2+ phase. In a manner similar to that for 1 microM nifedipine, TTX also delayed the onset of the other phases. Thus, we hypothesize that MeHg depolarizes the plasma membrane leading to an increase in the activation of voltage-dependent Na+ and Ca2+ channels which promotes, directly or indirectly, the influx of Ca2+ during the second Ca2+ phase.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Hare MF,Atchison WDdoi
10.1006/taap.1995.1236subject
Has Abstractpub_date
1995-12-01 00:00:00pages
299-307issue
2eissn
0041-008Xissn
1096-0333pii
S0041-008X(85)71236-7journal_volume
135pub_type
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