Mice with disrupted BK channel β1 subunit gene feature abnormal Ca2+ spark/STOC coupling and elevated blood pressure

Large-conductance potassium (BK) channels in vascular smooth muscle cells (VSMCs) sense both changes in membrane potential and in intracellular Ca2+ concentration. BK channels may serve as negative feedback regulators of vascular tone by linking membrane depolarization and local increases in intracellular Ca2+ concentration (Ca2+ sparks) to repolarizing spontaneous transient outward KC currents (STOCs). BK channels are composed of channel-forming BK alpha and auxiliary BK beta1 subunits, which confer to BK channels an increased sensitivity for changes in membrane potential and Ca2+. To assess the in vivo functions of this beta subunit, mice with a disrupted BK beta1 gene were generated. Cerebral artery VSMCs from BK beta1 -/- mice generated Ca2+ sparks of normal amplitude and frequency, but STOC frequencies were largely reduced at physiological membrane potentials. Our results indicate that BK beta1 -/- mice have an abnormal Ca2+ spark/STOC coupling that is shifted to more depolarized potentials. Thoracic aortic rings from BK beta1 -/- mice responded to agonist and elevated KCl with an increased contractility. BK beta1 -/- mice had higher systemic blood pressure than BK beta1 +/+ mice but responded normally to alpha (1)-adrenergic vasoconstriction and nitric oxide-mediated vasodilation. We propose that the elevated blood pressure in BK beta1 -/- mice serves to normalize Ca2+ spark/STOC coupling for regulating myogenic tone. The full text of this article is available at http://www.circresaha.org.