Effects of calcium channel antagonists on calcium entry and glutamate release from cultured rat cerebellar granule cells.
Using a range of Ca2+ channel blockers we have investigated the Ca2+ channel subtypes that mediate the depolarisation-induced elevation of the intracellular free Ca2+ concentration ([Ca2+]i) and glutamate release from cultured rat cerebellar granule cells. omega-Conotoxin-GVIA had little effect on either the transient or plateau phase of the depolarisation-induced [Ca2+]i rise or on glutamate release, ruling out a significant role for N-type Ca2+ channels. Nifedipine substantially inhibited the initial transient rise in [Ca2+]i and the plateau phase of the [Ca2+]i rise and glutamate release, suggesting the involvement of L-type Ca2+ channels. Both omega-agatoxin and omega-conotoxin-MVIIC also inhibited the transient rise in [Ca2+]i and glutamate release but not the plateau phase of the [Ca2+]i rise. The inhibitions by nifedipine were not increased by coaddition of omega-conotoxin-MVIIC, suggesting overlapping sensitivity to these channel blockers. These data show that glutamate release from granule cells in response to depolarisation with a high KCI level involves Ca2+ currents that are sensitive to nifedipine, omega-agatoxin-IVA, and also omega-conotoxin-MVIIC. The overlapping sensitivity of the channels to these toxins prevents attribution of any of the phases of the [Ca2+]i rise or glutamate release to distinct P-, Q-, or O-type Ca2+ currents.
Graham
M E
ME
Physiological Laboratory, University of Liverpool, England, U.K.
Burgoyne
R D
RD
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004594:Electrophysiology; D005470:Fluorometry; D016257:Fura-2; D018698:Glutamic Acid / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013111:Spider Venoms / Q000494:pharmacology; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010455:Peptides; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; D018698:Glutamic Acid; D002118:Calcium; D016257:Fura-2