Mice with disrupted BK channel beta1 subunit gene feature abnormal Ca(2+) spark/STOC coupling and elevated blood pressure

Circ Res. 2000 Nov 24;87(11):E53-60. doi: 10.1161/01.res.87.11.e53.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Signaling / genetics*
  • Cells, Cultured
  • Cerebral Arteries / metabolism
  • Female
  • Gene Targeting
  • Homozygote
  • Hypertension / genetics*
  • Hypertension / metabolism*
  • In Vitro Techniques
  • Large-Conductance Calcium-Activated Potassium Channels
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Smooth, Vascular / metabolism
  • Potassium / metabolism*
  • Potassium Channels / deficiency
  • Potassium Channels / genetics*
  • Potassium Channels / metabolism
  • Potassium Channels, Calcium-Activated*
  • Potassium Chloride / pharmacology
  • Protein Subunits
  • RNA, Messenger / metabolism
  • Sequence Analysis, DNA
  • Signal Transduction / genetics*
  • Vasoconstriction / drug effects
  • Vasoconstriction / genetics
  • Vasodilator Agents / pharmacology


  • Large-Conductance Calcium-Activated Potassium Channels
  • Potassium Channels
  • Potassium Channels, Calcium-Activated
  • Protein Subunits
  • RNA, Messenger
  • Vasodilator Agents
  • Potassium Chloride
  • Potassium