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(Circulation Research. 1996;79:881-886.)
© 1996 American Heart Association, Inc.

Articles

Role of Ca²⁺-Activated K⁺ Channels in the Regulation of Membrane Potential and Tone of Smooth Muscle in Human Pial Arteries

Natalia I. Gokina, Theresa D. Wellman, Rosemary D. Bevan, Carrie L. Walters, Paul L. Penar, John A. Bevan

the Totman Laboratory for Human Cerebrovascular Research, Departments of Pharmacology (N.I.G., T.D.W., R.D.B., J.A.B.) and Neurosurgery (P.L.P.), University of Vermont, College of Medicine, Burlington; and Neurological Surgeons (C.L.W.), Phoenix, Ariz.

Correspondence to Natalia I. Gokina, Department of Obstetrics and Gynecology, University of Vermont, College of Medicine, Burlington, VT 05405.

Smooth muscle cells (SMCs) in 58% of human pial arteries obtained during surgery showed no spontaneous contractions and displayed a stable resting membrane potential (MP) of -54.7±1.5 mV. Those that exhibited periodic spontaneous contractions associated with periodic depolarization and generation of spontaneous action potentials (APs) had a less negative MP of -43.1±0.5 mV (42%). Inhibition of calcium-activated potassium (K_Ca) channels in the silent arteries by charybdotoxin (CTX) and tetraethylammonium ions (TEA) induced dose-dependent depolarization, AP generation, and contraction. TEA and CTX enhanced the spontaneous depolarization and force in arteries that exhibited spontaneous activity. They also prolonged the spontaneous APs up to several times and increased their upstroke amplitude. Both TEA and CTX failed to produce significant depolarization in arteries treated with nifedipine. It is concluded that K_Ca channels are important regulators of human pial artery SMC resting MP and tone. They are also involved in the control of AP amplitude and duration and the associated contractions. These data suggest that alterations in the activity of SMC K_Ca channels could be responsible for the appearance of spontaneous activity in human pial arteries in vitro and that impaired function of these channels might be related to vasospastic phenomena in human cerebral circulation.

Key Words: human cerebral arteries • membrane potential • action potentials • calcium-activated potassium channels • charybdotoxin

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