INCREASED ACTIVATION OF L-TYPE VOLTAGE-DEPENDENT CALCIUM CHANNELS IS ASSOCIATED WITH GLYCINE ENHANCEMENT OF N-METHYL-D-ASPARTATE-STIMULATEDDOPAMINE RELEASE IN GLOBAL CEREBRAL ISCHEMIA REPERFUSION/

We investigated the relationships among N-methyl-D-aspartate, glycine, L-type voltage-dependent calcium channels, and [H-3]dopamine release in a canine model of global cerebral ischemia/reperfusion. The binding of [H-3]PN200-110 ([H-3]isradipine) to L-type voltage-dependent calci um channels, that open as a consequence of N-methyl-D-aspartate-induce d changes in membrane potential, was approximately doubled in striatal membranes prepared from ischemic animals relative to controls, and re mained significantly elevated at 30 min and 2 h of reperfusion. These changes coincided temporally with changes in the ability of the voltag e-sensitive calcium channel blocker nitrendipine to inhibit glycine en hancement of N-methyl-D-aspartate-stimulated [H-3]dopamine release in striatal slices prepared from the same animals. Compared with nonische mic controls, N-methyl-D-aspartate-stimulated [H-3]dopamine release wa s increased in ischemic animals and remained increased throughout repe rfusion up to at least 24 h. Glycine enhanced N-methyl-D-aspartate-sti mulated release in all treatment groups. The enhancement of N-methyl-D -aspartate-stimulated dopamine release by glycine was reduced by the i nclusion of nitrendipine in striatal slices from ischemic and 30-min r eperfused animals. These data suggest that glycine may facilitate open ing of the voltage-dependent calcium channels activated by N-methyl-D- aspartate and that this facilitation is blocked by the antagonist nitr endipine.