A Ca2+-activated K+ channel from rabbit aorta: modulation by cromakalim.
A large conductance Ca2+-activated K+ channel from rabbit aorta was incorporated into planar lipid bilayers. This channel had a conductance of 337 +/- 7 pS in symmetrical 250 mM KCl solutions and had a Na+/K+ permeability ratio of less than 0.04. In asymmetrical solutions containing 300 mM KCl cis (intracellular), 100 mM KCl trans (extracellular) or 100 mM KCl cis 500 mM KCl trans, the reversal potentials for the channel were -30 and +46 mV, respectively. This channel possessed voltage-dependent activation and cis (intracellular) Ca2+ sensitivity. Cromakalim (50 nM) added to the trans side of the bilayer significantly increased the Popen by 56% from 0.09 +/- 0.01 to 0.14 +/- 0.01 (P less than 0.01) at -40 mV without altering the single channel conductance. This effect was dose-dependent, increasing at higher cromakalim concentrations. The primary effect of cromakalim was to decrease the tau slow of the channel closed state from 266 +/- 32 to 147 +/- 17 ms which is sufficient to account for the increase in Popen of the channel in the presence of cromakalim.
Gelband
C H
CH
Department of Pharmacology, University of Miami School of Medicine, FL 33101.
Lodge
N J
NJ
Van Breemen
C
C
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001578:Benzopyrans / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology*; D019806:Cromakalim; D004347:Drug Interactions; D066298:In Vitro Techniques; D007700:Kinetics; D008051:Lipid Bilayers / Q000032:analysis; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010276:Parasympatholytics / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology*; D011817:Rabbits
D001578:Benzopyrans; D008051:Lipid Bilayers; D010276:Parasympatholytics; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D002118:Calcium