Differential distribution and functional impact of BK channel beta1 subunits across mesenteric, coronary, and different cerebral arteries of the rat

• Published in: Pflügers Archiv 2017-02, Vol.469 (2), p.263-277
• Main Authors: Kuntamallappanavar, Guruprasad, Bisen, Shivantika, Bukiya, Anna N., Dopico, Alex M.
• Format: Article
• Language: English
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Blood Pressure - physiology; Cell Biology; Cerebral Arteries - metabolism; Coronary Vessels - metabolism; Human Physiology; Ion Channels; Large-Conductance Calcium-Activated Potassium Channel beta Subunits - metabolism; Male; Mesenteric Arteries - metabolism; Molecular Medicine; Muscle Cells - metabolism; Muscle Contraction - physiology; Muscle, Smooth, Vascular - metabolism; Neurosciences; Rats; Rats, Sprague-Dawley; Receptors; Receptors and Transporters; Vasodilation - physiology
• ISSN: 0031-6768; 1432-2013
• DOI: 10.1007/s00424-016-1929-z

Large conductance, Ca 2+ i - and voltage-gated K + (BK) channels regulate myogenic tone and, thus, arterial diameter. In smooth muscle (SM), BK channels include channel-forming α and auxiliary β1 subunits. BK β1 increases the channel’s Ca 2+ sensitivity, allowing BK channels to negatively feedback on depolarization-induced Ca 2+ entry, oppose SM contraction and favor vasodilation. Thus, endothelial-independent vasodilation can be evoked though targeting of SM BK β1 by endogenous ligands, including lithocholate (LCA). Here, we investigated the expression of BK β1 across arteries of the cerebral and peripheral circulations, and the contribution of such expression to channel function and BK β1-mediated vasodilation. Data demonstrate that endothelium-independent, BK β1-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 β1 functional presence. Indeed, in the absence of detectable changes in BK α, BA and CA myocytes showed an increased location of BK β1 in the plasmalemma/subplasmalemma. Moreover, these myocytes distinctly showed increased BK β1 messenger RNA (mRNA) levels. Supporting a major role of enhanced BK β1 transcripts in artery dilation, LCA-induced dilation of MCA transfected with BK β1 complementary DNA (cDNA) was as high as LCA-induced dilation of untransfected BA or CA.