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Increased Activation of L‐Type Voltage‐Dependent Calcium Channels Is Associated with Glycine Enhancement of N ‐Methyl‐ d ‐Aspartate‐Stimulated Dopamine Release in Global Cerebral Ischemia/Reperfusion
Author(s) -
Werling Linda L.,
Hoehner Paul J.,
Hurt K. Joseph,
Fox Laura G.,
Blanck Thomas J. J.,
Rosenthal Robert E.,
Fiskum Gary
Publication year - 1994
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1994.63010215.x
Subject(s) - nitrendipine , dopamine , chemistry , glycine , isradipine , voltage dependent calcium channel , calcium , endocrinology , medicine , calcium channel , antagonist , pharmacology , biophysics , biochemistry , biology , receptor , amino acid
Abstract: We investigated the relationships among N ‐methyl‐ d ‐aspartate, glycine, L‐type voltage‐dependent calcium channels, and [ 3 H]dopamine release in a canine model of global cerebral ischemia/reperfusion. The binding of [ 3 H]PN200‐110 ([ 3 H]isradipine) to L‐type voltage‐dependent calcium channels, that open as a consequence of N ‐methyl‐ d ‐aspartate‐induced changes in membrane potential, was approximately doubled in striatal membranes prepared from ischemic animals relative to controls, and remained significantly elevated at 30 min and 2 h of reperfusion. These changes coincided temporally with changes in the ability of the voltage‐sensitive calcium channel blocker nitrendipine to inhibit glycine enhancement of N ‐methyl‐ d ‐aspartate‐stimulated [ 3 H]dopamine release in striatal slices prepared from the same animals. Compared with nonischemic controls, N ‐methyl‐ d ‐aspartate‐stimulated [ 3 H]dopamine release was increased in ischemic animals and remained increased throughout reperfusion up to at least 24 h. Glycine enhanced N ‐methyl‐ d ‐aspartate‐stimulated release in all treatment groups. The enhancement of N ‐methyl‐ d ‐aspartate‐stimulated dopamine release by glycine was reduced by the inclusion of nitrendipine in striatal slices from ischemic and 30‐min reperfused animals. These data suggest that glycine may facilitate opening of the voltage‐dependent calcium channels activated by N ‐methyl‐ d ‐aspartate and that this facilitation is blocked by the antagonist nitrendipine.