Inward rectifier K+ currents in smooth muscle cells from rat coronary arteries: block by Mg2+, Ca2+, and Ba2+

Abstract

Inward rectifier K+ channels have been implicated in the control of membrane potential and external K(+)-induced dilations of small coronary arteries. To identify and characterize inward rectifier K+ currents in coronary artery smooth muscle, whole cell K+ currents in smooth muscle cells enzymatically isolated from rat coronary (septal) arteries (diameters, 100-150 microns) were measured in the conventional and perforated configurations of the patch-clamp technique. Ba(2+)-sensitive, whole cell K+ current-voltage relationships exhibited inward rectification. Blockers of Ca(2+)-activated K+ channels (1 mM tetraethylammonium ion), ATP-sensitive K+ channels (10 microM glibenclamide), and voltage-dependent K+ channels (1 mM 4-aminopyridine) in smooth muscle did not affect inward rectifier K+ currents. The nonselective K+ channel inhibitor phencyclidine (100 microM) reduced inward rectifier K+ currents by approximately 50%. External Ba2+ reduced inward currents, with membrane potential hyperpolarization increasing inhibition. The half-inhibition constant for Ba2+ was 2.1 microM at -60 mV, decreasing e-fold for a 25-mV hyperpolarization. External Cs+ also blocked inward rectifier K+ currents, with the half-inhibition constant for Cs+ of 2.9 mM at -60 mV. External Ca2+ and Mg2+ reduced inward rectifier K+ currents. At -60 mV, Ca2+ and Mg2+ (1 mM) reduced inward currents by 33 and 21%, respectively. Inward rectification was not affected by dialysis of the cell's interior with a nominally Ca(2+)- and Mg(2+)-free solution. These findings indicate that inward rectifier K+ channels exist in coronary artery smooth muscle and that Ba2+ may be a useful probe for the functional role of inward rectifier K+ channels in coronary arteries.