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(Circulation Research. 2000;87:e53.)
© 2000 American Heart Association, Inc.

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Mice With Disrupted BK Channel ß1 Subunit Gene Feature Abnormal Ca²⁺ Spark/STOC Coupling and Elevated Blood Pressure

Saskia Plüger, Jörg Faulhaber, Michael Fürstenau, Matthias Löhn, Ralph Waldschütz, Maik Gollasch, Hermann Haller, Friedrich C. Luft, Heimo Ehmke, Olaf Pongs

From the Institut für Neurale Signalverarbeitung (S.P., R.W., O.P.), ZMNH, Universität Hamburg, Hamburg, Germany; Franz-Volhard-Klinik am Max-Delbrück-Centrum für Molekulare Medizin (M.F., M.L., M.G., H.H., F.C.L.), Humboldt Universität zu Berlin, Berlin, Germany; and Institut für Physiologie (J.F., H.E.), Universität Hamburg, Hamburg, Germany.

Correspondence to Prof Dr O. Pongs, Zentrum für Molekulare Neurobiologie der Universität Hamburg, Institut für Neurale Signalverarbeitung, Martinistrasse 52, D-20246 Hamburg, Germany. E-mail pointuri{at}uke.uni-hamburg.de

Abstract—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 K⁺ currents (STOCs). BK channels are composed of channel-forming BK and auxiliary BKß1 subunits, which confer to BK channels an increased sensitivity for changes in membrane potential and Ca²⁺. To assess the in vivo functions of this ß subunit, mice with a disrupted BKß1 gene were generated. Cerebral artery VSMCs from BKß1 -/- mice generated Ca²⁺ sparks of normal amplitude and frequency, but STOC frequencies were largely reduced at physiological membrane potentials. Our results indicate that BKß1 -/- mice have an abnormal Ca²⁺ spark/STOC coupling that is shifted to more depolarized potentials. Thoracic aortic rings from BKß1 -/- mice responded to agonist and elevated KCl with an increased contractility. BKß1 -/- mice had higher systemic blood pressure than BKß1 +/+ mice but responded normally to ₁-adrenergic vasoconstriction and nitric oxide–mediated vasodilation. We propose that the elevated blood pressure in BKß1 -/- 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.

Key Words: hypertension • potassium channels • spontaneous transient outward K⁺ currents • vasoconstriction

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