Modulation of maxi-k channels by voltage-dependent calcium channels
and methacholine in single airway smooth muscle cells.
Kotlikoff, Yong-Xiao Wang Bernd K. Fleischmann & Michael I.
Department of Animal Biology, School of Veterinary Medicine,
University of Pennsylvania, Philadelphia, PA 19104-6046, U.S.A.
APStracts 3:0325C, 1996.
The role of Ca2+ influx through voltage-dependent Ca2+ channels (VDCC)
and the inhibitory effects of methacholine on Ca2+-activated
potassium channels were studied in voltage-clamped (nystatin), fura-2
loaded airway smooth muscle cells. Spontaneous transient outward
currents (STOCs) were strongly coupled to VDCC activity; activity was
suppressed by nisoldipine and Cd2+ and increased by Bay K8644 within
seconds. Moreover, release of intracellular calcium by caffeine or
cyclopiazonic acid only partially suppressed STOCs, and the remainder
were almost completely blocked by nisoldipine. Methacholine
suppressed STOCs, but also significantly decreased the mean outward
current. Whole-cell current inhibition was observed in the presence
of 4-aminopyridine, but not in the presence of charybdotoxin.
Caffeine inhibited STOCs, but macroscopic outward currents were not
altered. In the continued presence of caffeine, methacholine
abolished the remaining STOCs and decreased the mean potassium
current. We conclude that STOCs are activated by influx of calcium
through plasmalemmal VDCC, as well as by release of calcium from
intracellular stores, and muscarinic stimulation depresses the mean
KCa current via a pathway independent of the depletion of
intracellular Ca2+ stores.
Received 29 May 1996; accepted in final form 11 October 1996.
APS Manuscript Number C303-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996