VOLTAGE-GATED CALCIUM CHANNELS IN CNS WHITE-MATTER - ROLE IN ANOXIC INJURY

被引:104
作者
FERN, R [1 ]
RANSOM, BR [1 ]
WAXMAN, SG [1 ]
机构
[1] DEPT VET AFFAIRS MED CTR,NEUROSCI RES CTR,W HAVEN,CT 06516
关键词
D O I
10.1152/jn.1995.74.1.369
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 mu M), diltiazem (50 mu M), and nifedepine (2.5 mu M) 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 mu M diltiazem and 1 mu M 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 mu M diltiazem + 1 mu M SNX-230 + 1 mu M SNX-124 failed to produce any additional increase in CAP recovery (71.3 +/- 5.6%, n = 8). Application of 1 mu M SNX-124 alone did not significantly protect against anoxic injury (CAP recovery, 36.3 +/- 2.9%, n = 10). 4. While N-type and L-type Ca2+ channels were involved in the development of anoxic injury, perfusion with 50 mu M diltiazem or 1-2 mu M SNX-124 had no effect on the normoxic CAP. Perfusion with 1 mu M SNX-230, however, produced a gradual increase in CAP area over 130 min. CAP area reached an average of 114.2 +/- 5.8% of the initial value (n = 8), compared with a reduction of CAP area to 88.9 +/- 5.13% of the initial value (n = 8) found after 130 min under control conditions (P < 0.005). 5. Concentrations of Co2+ and Cd2+ known to block Ca2+ channels irreversibly reduced CAP area. This effect of Cd2+ and Co2+ was potentiated by co-perfusion with 30 mM K+. Low concentrations of Cd2+ (2 mu M) and Co2+ (200 mu M), which were below concentrations that reduced CAP area in 30 mM K+, had a protective action against anoxic injury but probably did not block the majority of Ca2+ channels. 6. We conclude that L-type and N-type Ca2+ channels are involved in the development of anoxic injury in CNS white matter. Ca2+ channels are therefore involved in anoxic injury in both CNS gray matter and white matter, suggesting that strategies directed against Ca2+ influx via Ca2+ channels may provide protection for a broad spectrum of CNS regions during stroke. In addition, we observed changes in the CAP following block of CgTx MVIIC-sensitive Ca2+ channels, indicating the presence of three pharmacologically distinct Ca2+ channels in CNS white matter.
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收藏
页码:369 / 377
页数:9
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