title: Mice with disrupted BK channel beta1 subunit gene feature abnormal Ca(2+) spark/STOC coupling and elevated blood pressure.
abstract: 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.
authors.affiliation: Institut für Neurale Signalverarbeitung, ZMNH, Universität Hamburg, Hamburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Plüger
authors.forename: J
authors.initials: J
authors.lastname: Faulhaber
authors.forename: M
authors.initials: M
authors.lastname: Fürstenau
authors.forename: M
authors.initials: M
authors.lastname: Löhn
authors.forename: R
authors.initials: R
authors.lastname: Waldschütz
authors.forename: M
authors.initials: M
authors.lastname: Gollasch
authors.forename: H
authors.initials: H
authors.lastname: Haller
authors.forename: F C
authors.initials: FC
authors.lastname: Luft
authors.forename: H
authors.initials: H
authors.lastname: Ehmke
authors.forename: O
authors.initials: O
authors.lastname: Pongs
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000235:genetics*; D002478:Cells, Cultured; D002536:Cerebral Arteries / Q000378:metabolism; D005260:Female; D018390:Gene Targeting; D006720:Homozygote; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism*; D066298:In Vitro Techniques; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated; D011189:Potassium Chloride / Q000494:pharmacology; D021122:Protein Subunits; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000235:genetics*; D014661:Vasoconstriction / Q000187:drug effects / Q000235:genetics; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D021122:Protein Subunits; D012333:RNA, Messenger; D014665:Vasodilator Agents; D011189:Potassium Chloride; D011188:Potassium