THE ROLE OF L-TYPE VOLTAGE-DEPENDENT CALCIUM CHANNELS IN STIMULATED [H-3] NOREPINEPHRINE RELEASE FROM CANINE HIPPOCAMPAL SLICES FOLLOWING GLOBAL CEREBRAL-ISCHEMIA AND REPERFUSION

The hippocampus is among those brain regions which are selectively vul nerable to ischemic damage. Hippocampal damage due to transient cerebr al ischemia is mainly of the delayed, non-necrotic type which may aris e after disruption or activation of specific cellular systems, includi ng transmitter release through excitatory amino acid receptors. We inv estigated the contribution of L-type voltage dependent calcium channel s (VDCCs) to glycine (GLY) potentiated N-methyl-D-aspartate (NMDA) rec eptor- and potassium-stimulated [H-3]norepinephrine (NE) release in a canine model of global cerebral ischemia and reperfusion. Tissue was c ollected from four experimental groups: non-arrested controls (NA), gl obal cerebral ischemia induced by 10 minute cardiac arrest (CA), and C A followed by 30 min or 24 hours reperfusion after restoration of spon taneous circulation. Brain slices prepared from all groups accumulated approximately equivalent amounts of [H-3]NE. The sensitivity of [H-3] NE release to stimulation by NMDA/GLY or elevated potassium was unchan ged after ischemia and reperfusion. About 30% of release stimulated by the addition of 20 mM potassium was inhibited by the NMDA receptor-op erated channel antagonist MK801 in all groups except CA in which only 4% of release was inhibited by MK801, The ability of 1 mu M nitrendipi ne (NTP) to block stimulated release indicated that the contribution o f the L-type VDCC to potassium or NMDA/GLY-stimulated release was sign ificant only in NA and 24 hour reperfused animals. These data suggest that NE release may be stimulated through the NMDA receptor channel at control levels for up to 24 hours after ischemic insult and that the L-type VDCC is not a significant mediator of Ca++-induced [H-3]NE rele ase in arrest and early reperfusion. The data also support the involve ment of the L-type VDCC in regulating NMDA-stimulated release in NA an d 24 hour reperfused animals. The results in hippocampus demonstrate a different pattern of L-type VDCC-mediated catecholamine release follo wing ischemia and reperfusion from that found for [H-3]dopamine releas e from canine striatal slices in our previous study.