CALCIUM-SENSITIVE POTASSIUM CURRENT IN ISOLATED CANINE CORONARY SMOOTH-MUSCLE CELLS

This study characterizes K+ current in canine coronary artery and inve stigates its role in regulation of vascular smooth muscle tone during the resting and activated state. Isolated rings and whole-cell K+ curr ent as well as single K+ channels were studied. Tetraethylammonium (<3 mM) did not increase the resting tension in isolated rings; however, 0.3 mM tetraethylammonium increased tension in vessels that were preco ntracted by elevated [K+](o) or 5-hydroxytryptamine (5-HT). The whole- cell K+ current showed voltage and Ca2+ dependency and sensitivity to tetraethylammonium (31 +/- 7, 72 +/- 2, and 83 +/- 4% depression by 1, 10, and 30 mM tetraethylammonium, respectively). A large-conductance (100 pS) K+ channel was identified in cell-attached patches with open- time distribution fitted with two exponentials. Calcium ionophore A231 87 (10 mu M) increased the probability of opening, mean open time, and amplitude of this channel in cell-attached patches, suggesting Ca2+ d ependency. A23187 shifted the plot of unitary current as a function of pipette potential to the right, suggesting A23187-induced cell hyperp olarization. In inside-out patches, increase in cytoplasmic-side [Ca2] from 10(-7) to 10(-6) M increased both the frequency of channel open ing and duration of the open state, without changing its conductance. Tetraethylammonium (1 mM) on the cytoplasmic side caused a reversible decrease in the current amplitude. Charybdotoxin (100 nM) decreased th e probability of opening and mean open time and increased mean closed time, while apamin (100 nM) did not significantly affect channel kinet ics. In summary, this study demonstrates the existence and important f unctional role of a large-conductance, Ca2+-sensitive K+ channel in re gulation of membrane potential and cell excitability, as well as some aspects of regulation and kinetics of this channel in canine coronary arterial cells.