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.