title: Activation of BKCa 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.
authors.affiliation: Department of Aerospace Physiology, Fourth Military Medical University, Xi'an 710032, China. jin-ma@fmmu.edu.cn
authors.forename: Man-Jiang
authors.initials: MJ
authors.lastname: Xie
authors.forename: Yu-Guang
authors.initials: YG
authors.lastname: Ma
authors.forename: Fang
authors.initials: F
authors.lastname: Gao
authors.forename: Yun-Gang
authors.initials: YG
authors.lastname: Bai
authors.forename: Jiu-Hua
authors.initials: JH
authors.lastname: Cheng
authors.forename: Yao-Ming
authors.initials: YM
authors.lastname: Chang
authors.forename: Zhi-Bin
authors.initials: ZB
authors.lastname: Yu
authors.forename: Jin
authors.initials: J
authors.lastname: Ma
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002536:Cerebral Arteries / Q000378:metabolism / Q000473:pathology; D019417:Hindlimb Suspension; D006801:Humans; D020287:In Situ Nick-End Labeling; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000378:metabolism; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits / Q000378:metabolism; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials; D008854:Microscopy, Electron; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection; D018474:Weightlessness Simulation
chemical_list: C494841:KCNMA1 protein, human; C531905:KCNMB1 protein, human; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D002118:Calcium