ANG II inhibits calcium-activated potassium channels from coronary smooth muscle in lipid bilayers.
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.
Toro
L
L
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030.
Amador
M
M
Stefani
E
E
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D003331:Coronary Vessels / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015640:Ion Channel Gating; D007700:Kinetics; D008051:Lipid Bilayers; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009994:Osmolar Concentration; D015221:Potassium Channels / Q000378:metabolism*; D013552:Swine; D013997:Time Factors
D008051:Lipid Bilayers; D015221:Potassium Channels; D000804:Angiotensin II; D002118:Calcium