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ANG II inhibits calcium-activated potassium channels from coronary smooth muscle in lipid bilayers

Am J Physiol. 1990 Mar;258(3 Pt 2):H912-5. doi: 10.1152/ajpheart.1990.258.3.H912.

Abstract

Angiotensin II (ANG II) is a powerful vasoconstrictor of coronary vessels and other smooth muscles. One of the actions of ANG II is the inhibition of K+ currents, possibly contributing to depolarization and contraction. Therefore, we investigated the role of ANG II on the regulation of K+ channels at the single-channel level. We studied its effect on calcium-activated potassium (KCa) channels (congruent to 250 pS) from coronary smooth muscle incorporated into lipid bilayers. KCa channels were sensitive to externally applied ANG II at voltages from -20 to -70 mV and pCa between 6.5 and 4. The dose-response curve gave a concentration of half-inhibition (Ki1/2) of 58 nM and a Hill coefficient of 2.2, indicating a minimum of two sites in the process. ANG II modified the open and closed states of the channel, affecting their proportions and their values. In addition, a new much slower (congruent to 1 s) closed or "blocked" state appeared. We conclude that one of the mechanisms by which ANG II causes vasoconstriction of the coronary vessels is a direct inhibition of KCa channels contributing to depolarization and contraction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiotensin II / pharmacology*
  • Animals
  • Calcium / pharmacology*
  • Coronary Vessels / metabolism*
  • Dose-Response Relationship, Drug
  • Ion Channel Gating
  • Kinetics
  • Lipid Bilayers
  • Muscle, Smooth, Vascular / metabolism*
  • Osmolar Concentration
  • Potassium Channels / metabolism*
  • Swine
  • Time Factors

Substances

  • Lipid Bilayers
  • Potassium Channels
  • Angiotensin II
  • Calcium