期刊
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
卷 469, 期 2, 页码 263-277出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00424-016-1929-z
关键词
MaxiK channel; BK beta 1 subunit; KCNMB1; Cerebral artery myocyte; Vasodilation; Vascular smooth muscle; Lithocholate
类别
资金
- American Heart Association Predoctoral Fellowship
- National Institutes of Health [R37AA11560, R01HL104631]
Large conductance, Ca-i-(2+) and voltage-gated K+ (BK) channels regulate myogenic tone and, thus, arterial diameter. In smooth muscle (SM), BK channels include channel-forming alpha and auxiliary beta 1 subunits. BK beta 1 increases the channel's Ca2+ sensitivity, allowing BK channels to negatively feedback on depolarization-induced Ca2+ entry, oppose SM contraction and favor vasodilation. Thus, endothelial-independent vasodilation can be evoked though targeting of SM BK beta 1 by endogenous ligands, including lithocholate (LCA). Here, we investigated the expression of BK beta 1 across arteries of the cerebral and peripheral circulations, and the contribution of such expression to channel function and BK beta 1-mediated vasodilation. Data demonstrate that endothelium-independent, BK beta 1-mediated vasodilation by LCA is larger in coronary (CA) and basilar (BA) arteries than in anterior cerebral (ACA), middle cerebral (MCA), posterior cerebral (PCA), and mesenteric (MA) arteries, all arterial segments having a similar diameter. Thus, differential dilation occurs in extracranial arteries which are subjected to similar vascular pressure (CA vs. MA) and in arteries that irrigate different brain regions (BA vs. ACA, MCA, and PCA). SM BK channels from BA and CA displayed increased basal activity and LCA responses, indicating increased BK beta 1 functional presence. Indeed, in the absence of detectable changes in BK alpha, BA and CA myocytes showed an increased location of BK beta 1 in the plasmalemma/subplasmalemma. Moreover, these myocytes distinctly showed increased BK beta 1messenger RNA (mRNA) levels. Supporting a major role of enhanced BK beta 1 transcripts in artery dilation, LCA-induced dilation of MCA transfected with BK beta 1 complementary DNA (cDNA) was as high as LCA-induced dilation of untransfected BA or CA.
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