The role of L-type voltage dependent calcium channels in stimulated [3H]norepinephrine release from canine hippocampal slices following global cerebral ischemia and reperfusion.
The hippocampus is among those brain regions which are selectively vulnerable to ischemic damage. Hippocampal damage due to transient cerebral ischemia is mainly of the delayed, non-necrotic type which may arise after disruption or activation of specific cellular systems, including transmitter release through excitatory amino acid receptors. We investigated the contribution of L-type voltage dependent calcium channels (VDCCs) to glycine (GLY) potentiated N-methyl-D-aspartate (NMDA) receptor- and potassium-stimulated [3H]norepinephrine (NE) release in a canine model of global cerebral ischemia and reperfusion. Tissue was collected from four experimental groups: non-arrested controls (NA), global cerebral ischemia induced by 10 minute cardiac arrest (CA), and CA followed by 30 min or 24 hours reperfusion after restoration of spontaneous circulation. Brain slices prepared from all groups accumulated approximately equivalent amounts of [3H]NE. The sensitivity of [3H]NE release to stimulation by NMDA/GLY or elevated potassium was unchanged after ischemia and reperfusion. About 30% of release stimulated by the addition of 20 mM potassium was inhibited by the NMDA receptor-operated channel antagonist MK801 in all groups except CA in which only 4% of release was inhibited by MK801. The ability of 1 microM nitrendipine (NTP) to block stimulated release indicated that the contribution of the L-type VDCC to potassium or NMDA/GLY-stimulated release was significant only in NA and 24 hour reperfused animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Hurt
K J
KJ
Department of Pharmacology, George Washington University Medical Center, Washington, DC 20037, USA.
Fiskum
G
G
Rosenthal
R E
RE
Werling
L L
LL
D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D015220:Calcium Channels; D004285:Dogs; D005260:Female; D006624:Hippocampus; D016202:N-Methylaspartate / Q000494:pharmacology; D009568:Nitrendipine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D015424:Reperfusion; D013997:Time Factors
D015220:Calcium Channels; D016202:N-Methylaspartate; D009568:Nitrendipine; D011188:Potassium; D009638:Norepinephrine