Mice with a disrupted BKbeta1 gene exhibited abnormal Ca2+ spark/STOC coupling, increased vascular contractility, and higher systemic blood pressure compared to wild-type mice.
Disruption of the BK channel beta1 subunit in mice leads to abnormal Ca2+ spark/STOC coupling and elevated systemic blood pressure, highlighting its role in regulating vascular tone.
Large-conductance potassium (BK) channels in vascular smooth muscle cells (VSMCs) sense both changes in membrane potential and in intracellular Ca(2+) concentration. BK channels may serve as negative feedback regulators of vascular tone by linking membrane depolarization and local increases in intracellular Ca(2+) concentration (Ca(2+) sparks) to repolarizing spontaneous transient outward K(+) currents (STOCs). BK channels are composed of channel-forming BKalpha and auxiliary BKbeta1 subunits, which confer to BK channels an increased sensitivity for changes in membrane potential and Ca(2+). To assess the in vivo functions of this ss subunit, mice with a disrupted BKbeta1 gene were generated. Cerebral artery VSMCs from BKbeta1 -/- mice generated Ca(2+) sparks of normal amplitude and frequency, but STOC frequencies were largely reduced at physiological membrane potentials. Our results indicate that BKbeta1 -/- mice have an abnormal Ca(2+) spark/STOC coupling that is shifted to more depolarized potentials. Thoracic aortic rings from BKbeta1 -/- mice responded to agonist and elevated KCl with a increased contractility. BKbeta1 -/- mice had higher systemic blood pressure than BKbeta1 +/+ mice but responded normally to alpha(1)-adrenergic vasoconstriction and nitric oxide-mediated vasodilation. We propose that the elevated blood pressure in BKbeta1 -/- mice serves to normalize Ca(2+) spark/STOC coupling for regulating myogenic tone. The full text of this article is available at http://www.circresaha.org.
Plüger et al. (Fri,) conducted a other in Elevated blood pressure. Disrupted BK channel beta1 subunit gene (BKbeta1 -/-) vs. Wild-type mice (BKbeta1 +/+) was evaluated on Ca2+ spark/STOC coupling and systemic blood pressure. Mice with a disrupted BKbeta1 gene exhibited abnormal Ca2+ spark/STOC coupling, increased vascular contractility, and higher systemic blood pressure compared to wild-type mice.