Properties of the cromakalim-induced potassium conductance in smooth muscle cells isolated from the rabbit portal vein.
1. Single smooth muscle cells were isolated freshly from the rabbit portal vein and membrane currents were recorded by the whole-cell or excised patch configurations of the patch-clamp technique at room temperature. 2. Cromakalim (Ckm, 10 microM) induced a potassium current (ICkm) that showed no pronounced voltage-dependence and had low current noise. 3. This current, ICkm, was inhibited by (in order of potency): phencyclidine greater than quinidine greater than 4-aminopyridine greater than tetraethylammonium ions (TEA). These drugs inhibited the delayed rectifier current, IdK, which is activated by depolarization of the cell, with the same order of potency. 4. Large conductance calcium-activated potassium channels (LKCa) in isolated membrane patches were blocked by (in order of potency) quinidine greater than TEA approximately phencyclidine. 4-Aminopyridine was ineffective. A similar order of potency was found for block of spontaneous transient outward currents thought to represent bursts of openings of LKCa channels. 5. The low current noise of ICkm at positive potentials, and its susceptibility to inhibitors indicated that it was not carried by LKCa channels, and that it may be carried by channels which underlie IdK. It was observed that when ICkm was activated, IdK was reduced. However, in two experiments, ICkm was much more susceptible to glibenclamide than IdK; possible reasons for this are discussed.
Beech
D J
DJ
Department of Pharmacology & Clinical Pharmacology, St. George's Hospital Medical School, London.
Bolton
T B
TB
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D019806:Cromakalim; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010276:Parasympatholytics / Q000494:pharmacology*; D011169:Portal Vein / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*; D011817:Rabbits
D001578:Benzopyrans; D007202:Indicators and Reagents; D010276:Parasympatholytics; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D002118:Calcium