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

• Published in: Journal of neurochemistry Vol. 63; no. 1; p. 215
• Main Authors: Werling, L L, Hoehner, P J, Hurt, K J, Fox, L G, Blanck, T J, Rosenthal, R E, Fiskum, G
• Format: Journal Article
• Language: English
• Published: England 01.07.1994
• Subjects: Animals; Brain Ischemia - metabolism; Calcium Channels - physiology; Dogs; Dopamine - metabolism; Female; Glycine - pharmacology; Isradipine - pharmacology; N-Methylaspartate - pharmacology; Nitrendipine - pharmacology; Reperfusion Injury - metabolism; Time Factors; Tritium
• ISSN: 0022-3042
• DOI: 10.1046/j.1471-4159.1994.63010215.x

We investigated the relationships among N-methyl-D-aspartate, glycine, L-type voltage-dependent calcium channels, and [3H]dopamine release in a canine model of global cerebral ischemia/reperfusion. The binding of [3H]PN200-110 ([3H]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 [3H]dopamine release in striatal slices prepared from the same animals. Compared with nonischemic controls, N-methyl-D-aspartate-stimulated [3H]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.