Activation of BK_Ca channel is associated with increased apoptosis of cerebrovascular smooth muscle cells in simulated microgravity rats

Abstract

Cerebral arterial remodeling is one of the critical factors in the occurrence of postspaceflight orthostatic intolerance. We hypothesize that large-conductance calcium-activated K(+) (BK(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(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(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(Ca) channel and apoptosis, channel protein and cell nucleus were double-stained. In cell studies, hSloalpha+beta1 channel was coexpressed into human embryonic kidney 293 (HEK293) cells to observe the effects of BK(Ca) channels on apoptosis. In rats, enhanced activities and expression of BK(Ca) channels were found to be correlated with increased apoptosis in cerebral VSMCs after simulated microgravity. In transfected HEK293 cells, activation of cloned BK(Ca) channel induced apoptosis, whereas inhibition of cloned BK(Ca) channel decreased apoptosis. In conclusion, activation of BK(Ca) channels is associated with increased apoptosis in cerebral VSMCs of simulated microgravity rats.

Chitosan oligosaccharide inhibits LPS-induced apoptosis of vascular endothelial cells through the BKCa channel and the p38 signaling pathway

“…However, the ion channel inhibitor iberiotoxin reverses these effects. Furthermore, in HEK293 cells which lack the BKCa channel, cell apoptosis was induced regardless of NS-1619 or iberiotoxin (14). This data provide support for the notion that BKCa is closely related to cell apoptosis.…”

“…9. Some studies have proven that most approaches of cell apoptosis are closely associated with the intracellular Ca 2+ overload (14). In addition, activation of the Toll-4 receptor by LPS may result in sarcoplasmic reticulum Ca 2+ release.…”

“…The BKCa channel, as a Ca 2+ -dependent potassium channel is sensitive to inflammatory cytokines. It has been reported that the BKCa channel may be activated by the stimulation of inflammatory cytokines, and alcohol, and that this activation may cause cell apoptosis (14). Furthermore, it has been shown that the chemical compound NS-1619 may accelerate the Ca 2+ release from the vascular smooth muscle cell calcium store and result in the increase of Ca 2+ concentration in cytoplasm (16).…”

Up-regulation of ryanodine receptor expression increases the calcium-induced calcium release and spontaneous calcium signals in cerebral arteries from hindlimb unloaded rats

“…In the same model, the reversibility of the vascular deconditioning induced by HU appeared after stopping the suspension protocol for 48 and 72 h after a duration of 7 and 14 days, respectively [28]. In cerebral arteries, we show here that the duration of 8 days is sufficient to induce a modulation in Ca 2+ signaling as observed at the level of BK Ca expression [48]. Here, we have clarified that the reversibility of the HU effect was already effective after 2 days following the end of the suspension protocol.…”

Activation of cloned BKCa channels in nitric oxide-induced apoptosis of HEK293 cells

“…Patch-clamp recordings were performed as previously described [16][17][18]. Whole-cell and single-channel of BK Ca currents were recorded with an amplifier (CEZ-2300, Nihon Kohden) and a version interface (Axon Instruments).…”