Role of Ca(2+)-activated K+ channels in the regulation of membrane potential and tone of smooth muscle in human pial arteries.
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 (KCa) 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 KCa 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 KCa 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.
Gokina
N I
NI
Totman Laboratory for Human Cerebrovascular Research, Department of Pharmacology, University of Vermont, College of Medicine, Burlington 05405, USA.
Wellman
T D
TD
Bevan
R D
RD
Walters
C L
CL
Penar
P L
PL
Bevan
J A
JA
D002118:Calcium / Q000378:metabolism*; D002536:Cerebral Arteries / Q000502:physiology*; D006801:Humans; D008564:Membrane Potentials; D009119:Muscle Contraction / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology*
D015221:Potassium Channels; D002118:Calcium