Voltage-gated calcium channels in CNS white matter: role in anoxic injury.
1. The effect of Ca2+ channel antagonists on the extent of anoxia-induced white matter injury was studied in the rat optic nerve, a white matter tract. Compound action potentials (CAPs) were recorded before and after a standard 60-min anoxic period to assess the extent of anoxic injury. 2. The L-type Ca2+ channel antagonists verapamil (90 microM), diltiazem (50 microM), and nifedepine (2.5 microM) significantly protected the rat optic nerve from anoxic injury. Mean recovery of CAP area was 51.3 +/- 3.0% (mean +/- SE, n = 8, P < 0.01), 65.6 +/- 5.3% (n = 8, P < 0.01), and 54.3 +/- 6.1% (n = 8, P < 0.01), respectively. Mean CAP recovery under control conditions was 35.2 +/- 0.3 (n = 33). 3. Simultaneous block of L-type and N-type Ca2+ channels by coapplication of 50 microM diltiazem and 1 microM SNX-124 [synthetic omega-conotoxin (CgTx) GVIA], resulted in postanoxic CAP recovery of 73.6 +/- 6.0% (n = 12), significantly larger than CAP recovery in diltiazem alone (P < 0.001). Block of CgTx MVIIC-sensitive channels in addition to L-type and N-type channels by coapplication of 50 microM diltiazem + 1 microM SNX-230 + 1 microM SNX-124 failed to produce any additional increase in CAP recovery (71.3 +/- 5.6%, n = 8). Application of 1 microM SNX-124 alone did not significantly protect against anoxic injury (CAP recovery, 36.3 +/- 2.9%, n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D004567:Electrodes, Implanted; D005260:Female; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D009900:Optic Nerve / Q000166:cytology / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D019831:Sodium-Calcium Exchanger; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002352:Carrier Proteins; D010455:Peptides; D019831:Sodium-Calcium Exchanger; D020866:omega-Conotoxin GVIA