Methylmercury affects multiple subtypes of calcium channels in rat cerebellar granule cells.
We tested the ability of methylmercury (MeHg) to block calcium channel current in cultures of neonatal cerebellar granule cells using whole-cell patch clamp techniques and Ba(2+) as charge carrier. Low micromolar concentrations of MeHg (0.25-1 microM) reduced the amplitude of whole cell Ba(2+) current in a concentration- and time-dependent fashion; however, this effect was not voltage-dependent and the current-voltage relationship was not altered. Increasing the stimulation frequency hastened the onset and increased the magnitude of block at both 0.25 and 0.5 microM MeHg but not at 1 microM. In the absence of stimulation, all concentrations of MeHg were able to decrease current amplitude. The ability of several Ca(2+) channel antagonists (omega-conotoxin GVIA, omega-conotoxin MVIIC, omega-agatoxin IVA, calcicludine, and nimodipine) to alter the MeHg-induced effect was tested in an effort to determine if MeHg targets a specific subtype of Ca(2+) channel. Each of the antagonists tested was able to decrease a portion of whole cell Ba(2+) current under control conditions. However, none were able to attenuate the MeHg-induced block of whole cell Ba(2+) current, suggesting either that the mechanism of MeHg-induced block involves sites other than those influenced specifically by Ca(2+) channel antagonists or that MeHg was able to "outcompete" these toxins for their binding sites. These results show that acute exposure to submicromolar concentrations of MeHg can block Ba(2+) currents carried through multiple Ca(2+) channel subtypes in primary cultures of cerebellar granule cells. However, it is unlikely that the presence of a specific Ca(2+) channel subtype is able to render granule cells more susceptible to the neurotoxicologic actions of MeHg.
Sirois
J E
JE
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan 48824-1317, USA.
Atchison
W D
WD
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects*; D004546:Elapid Venoms / Q000494:pharmacology; D008767:Methylmercury Compounds / Q000633:toxicity*; D051381:Rats; D020867:omega-Agatoxin IVA / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology; D020960:omega-Conotoxins / Q000494:pharmacology
D015220:Calcium Channels; D004546:Elapid Venoms; D008767:Methylmercury Compounds; C085673:calcicludin; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; D020866:omega-Conotoxin GVIA