Regulation of spontaneous transient outward potassium currents in human coronary arteries

Circulation
R BychkovHermann Haller

Abstract

Spontaneous transient outward potassium currents (STOCs) induce myogenic relaxation in small cerebral vessels. We found STOCs in human coronary artery vascular smooth muscle cells (VSMCs) and studied their regulation. K+ currents were recorded in human coronary VSMCs by current- and voltage-clamp techniques. STOCs were recorded in the presence of 200 mumol/L Cd2+ and 10 mumol/L verapamil, which block voltage-dependent Ca2+ channels. STOCs were inhibited by iberiotoxin (100 nmol/L), a selective blocker of Ca(2+)-activated potassium channels (BKCa), and disappeared in a Ca(2+)-free bath. Iberiotoxin depolarized the VSMCs within 20 minutes from -44 +/- 7 to -18 +/- 5 mV (n = 17). The Ca2+ ionophore A23187 increased intracellular Ca2+ and stimulated whole-cell BKCa current. Depletion of Ca2+ from the sarcoplasmic reticulum with caffeine (4 mmol/L) abolished STOCs for several minutes. Ryanodine (50 mumol/L) transiently stimulated STOCs but then completely inhibited STOCs within 10 minutes. The firing frequency of STOCs was directly correlated with intracellular Na+ concentrations from 0 to 24 mmol/L. Lowering intracellular Na+ to zero abolished STOCs. We next gave monensin (30 mumol/L) to increase intracellular Na+. This maneuver re...Continue Reading

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