Activation of [BK.sub.Ca] channel is associated with increased apoptosis of cerebrovascular smooth muscle cells in simulated microgravity rats

Cerebral arterial remodeling is one of the critical factors in the occurrence of postspaceflight orthostatic intolerance. We hypothesize that large-conductance calcium-activated [K.sup.+] ([BK.sub.Ca]) channels in vascular smooth muscle cells (VSMCs) may play an important role in regulating cerebrovascular adaptation during microgravity exposure. The aim of this work was to investigate whether activation of [BK.sub.Ca] channels is involved in regulation of apoptotic remodeling of cerebral arteries in simulated microgravity rats. In animal studies, Sprague-Dawley rats were subjected to 1-wk hindlimb unweighting to simulate microgravity. Alterations of [BK.sub.Ca] channels in cerebral VSMCs were investigated by patch clamp and Western blotting; apoptosis was assessed by electron microscopy and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling (TUNEL). To evaluate the correlation of [BK.sub.Ca] channel and apoptosis, channel protein and cell nucleus were double-stained. In cell studies, hSlo[alpha]+[beta]1 channel was coexpressed into human embryonic kidney 293 (HEK293) cells to observe the effects of [BK.sub.Ca] channels on apoptosis. In rats, enhanced activities and expression of [BK.sub.Ca] channels were found to be correlated with increased apoptosis in cerebral VSMCs after simulated microgravity. In transfected HEK293 cells, activation of cloned [BK.sub.Ca] channel induced apoptosis, whereas inhibition of cloned [BK.sub.Ca] channel decreased apoptosis. In conclusion, activation of [BK.sub.Ca] channels is associated with increased apoptosis in cerebral VSMCs of simulated microgravity rats. hindlimb unweighting; cerebral artery; human embryonic kidney 293 cells; cardiovascular remodeling doi: 10.1152/ajpcell.00474.2009.