L-type calcium channel blockade mechanisms of panaxadiol saponins against anoxic damage of cerebral cortical neurons isolated from rats.

AIM

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.

CONCLUSION

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.