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(Circulation. 1997;95:503-510.)
© 1997 American Heart Association, Inc.

Articles

Regulation of Spontaneous Transient Outward Potassium Currents in Human Coronary Arteries

Rostislav Bychkov, PhD; Maik Gollasch, MD, PhD; Christian Ried, MS; Friedrich C. Luft, MD; Hermann Haller, MD

the Franz Volhard Clinic and the Max-Delbruck Center for Molecular Medicine, Virchow Clinic, Humboldt University of Berlin, Germany.

Correspondence to Friedrich C. Luft, MD, Franz Volhard Clinic, Wiltberg Str 50, Berlin, Germany. E-mail fcluft{at}orion.rz.mdc-berlin.de

Background 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.

Methods and Results K⁺ currents were recorded in human coronary VSMCs by current- and voltage-clamp techniques. STOCs were recorded in the presence of 200 µmol/L Cd²⁺ and 10 µmol/L verapamil, which block voltage-dependent Ca²⁺ channels. STOCs were inhibited by iberiotoxin (100 nmol/L), a selective blocker of Ca²⁺-activated potassium channels (BK_Ca), and disappeared in a Ca²⁺-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 BK_Ca current. Depletion of Ca²⁺ from the sarcoplasmic reticulum with caffeine (4 mmol/L) abolished STOCs for several minutes. Ryanodine (50 µmol/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 µmol/L) to increase intracellular Na⁺. This maneuver resulted in an increase in whole-cell current fluctuations and STOCs. Monensin-induced STOCs were abolished by either lowering extracellular Ca²⁺ to zero or chelating Ca²⁺ intracellularly with BAPTA-AM (30 µmol/L).

Conclusions STOCs resulted from BK_Ca activity and were dependent on extracellular Ca²⁺ but not significantly on voltage-dependent Ca²⁺ channels. STOCs were dependent on intracellular Na⁺ and intracellular calcium store refilling state. We suggest that Ca²⁺ entry into the cell through reverse-mode Na⁺/Ca²⁺ exchange determines calcium store refilling, which in turn regulates STOC generation in human coronary VSMCs.

Key Words: potassium • calcium • cells • muscle, smooth

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