Differential Expression of BK Channel Alpha and Beta1 Subunits in Rat Cerebral Arteries

Abstract

Large conductance, Ca2+i/voltage-gated K+ channels (BK) regulate several physiological processes (Dopico et al., 2012). Native BK complexes consist of channel-forming α and auxiliary β subunits. Four β subunit types were identified, with β1 being highly expressed in smooth muscle (Brenner et al., 2000). BK β1 modifies the channel response to ligands: it increases the apparent Ca2+ sensitivity, mediates channel activation by cholanes (Brenner et al., 2000; Bukiya et al., 2009) and controls cerebral artery tone modification by selective ligands, including lithocholate (Bukiya et al., 2007; 2013). Here, we studied the expression of BK α and β1 subunits across basilar, anterior, middle and posterior cerebral arteries, and the possible contribution of their expression to channel phenotype and cerebral artery diameter response to lithocholate. Methods included quantitative real-time PCR, confocal microscopy, smooth muscle patch-clamp electrophysiology, and diameter determination of in vitro pressurized cerebral arteries. Results demonstrate: 1) BK α and β1 mRNA transcripts are expressed at higher levels in basilar arteries; 2) BK α protein surface levels in myocyte membranes are similar across the different intracranial territories while β1 levels are higher in basilar artery; 3) BK channel activity is also higher in myocytes from basilar arteries; 4) myocyte BK channels in basilar arteries show the highest response to lithocholate; 5) lithocholate-induced dilation of basilar arteries is significantly higher than those measured in other intracranial territories. Collectively, our results demonstrate differential BK β1 expression, as well as its contribution to BK current phenotype and vasodilation by lithocholate, across the major branches of the Willis’ circle. In particular, basilar arteries seem to be highly sensitive to vasoactive agents that act via BK β1 subunits.Support: HL104631 and AA11560 (AMD), and AHA Predoctoral Fellowship (GK).