L-type calcium channel blockade mechanisms of panaxadiol saponins against anoxic damage of cerebral cortical neurons isolated from rats.
OBJECTIVE
To identify the changes of L-type Ca2+ channel on cerebral cortical neurons of rats during anoxia and the protective mechanisms of panaxadiol saponins (PDS) against anoxic injury.


METHODS
Patch-clamp technique of cell-attached configuration and in vitro cerebral anoxic modle built with actuely isolated cortical cells of Wistar rats.


RESULTS
The open time of L-type Ca2+ channel of cortical neurons increased significantly from (2.85 +/- 0.21) ms to (9.1 +/- 1.0) ms (P < 0.01) under anoxia. The particular change was a long-lasting open, which was more than 20 ms in some cases. At the same time, the close time decreased from (38 +/- 8) ms to (10 +/- 3) ms (P < 0.01) and the open-state probability raised from (0.047 +/- 0.008) to (0.165 +/- 0.025) (P < 0.01). PDS (1.5 g.L-1) inhibited the activity of L-type Ca2+ channel both in normal and anoxic condition [open time from (2.23 +/- 0.47) ms and (9.1 +/- 1.0) ms to (1.03 +/- 0.25) ms and (2.1 +/- 0.4) ms; close time from (38 +/- 10) ms and (10 +/- 3) ms to (74 +/- 16) ms and (46 +/- 10 ms); open-state probability from (0.043 +/- 0.006) and (0.165 +/- 0.025) to (0.012 +/- 0.004) and (0.021 +/- 0.009), respectively, P all < 0.01]. The results of PDS were similar to those of verapamil, but were weaker compared with verapamil.


CONCLUSIONS
The L-type Ca2+ channels of rat cerebral cortical neurons were obviously opened during anoxia. The channels in normal and anoxic condition were effectively blocked by PDS. It was one of the important mechanisms by which PDS protected brain from the anoxic injury.
Kai
L
L
Department of Pharmacology, Third Military Medical University, Chongqing, China.
Wang
Z F
ZF
Xiao
J S
JS
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D015687:Cell Hypoxia; D002540:Cerebral Cortex / Q000166:cytology*; D036145:Ginsenosides; D066298:In Vitro Techniques; D009474:Neurons; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D014315:Triterpenes / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D036145:Ginsenosides; D014315:Triterpenes; C004564:panaxadiol; D014700:Verapamil