Differential Expression of BK Channel Beta1 Subunits in Rat Mesenteric, Coronary and Cerebral Arteries

Abstract

Large conductance, Ca2+i/voltage-gated K+ (BK) channels regulate several physiological processes (Yang et et al., 2015). In smooth muscle, BK complexes include channel-forming α and auxiliary β1 subunits (Brenner et al., 2000). BK β1 increases the channel's apparent Ca2+ sensitivity (Brenner et al.,2000) and is required for channel activation by lithocholate (LCA)(Bukiya et al., 2009). Here, we studied the expression of BK α and β1 subunits in mesenteric, coronary and cerebral (anterior, middle, posterior and basilar) arteries, and the contribution of such differential expression to LCA-induced artery dilation. Thus, we conducted quantitative real-time PCR, fluorescence confocal imaging and patch-clamp electrophysiology on freshly isolated cerebral artery myocytes, and diameter determination of arteries pressurized in vitro. Data show that: 1) BK α mRNA is higher in cerebral anterior and basilar arteries. In turn, β1 mRNA is higher in basilar and coronary arteries; 2) BK α protein levels at the myocyte membrane surface are similar across the different arteries whereas β1 levels are higher in basilar and coronary arteries; 3) BK channel basal activity is also higher in basilar and coronary artery myocytes; 4) Likewise, BK channels from basilar and coronary artery myocytes are more responsive to LCA; 5) Finally, LCA-induced dilation of basilar and coronary arteries is higher than dilation of other arteries. Our results demonstrate a differential protein expression and functional impact on both basal channel activity and its response to LCA, of BK β1 subunits across arteries from cerebral and systemic vasculatures. In particular, basilar and coronary artery myocytes show an increased biochemical and functional presence of BK β1 subunits, suggesting that these vascular territories are more susceptible to modulation via BK β1. Support: HL104631, R37AA11560 (AMD); AHA Pre-doctoral Fellowship (GK).