Atp activates k and cl channels via purinoceptor-mediated release
of ca2+ in human coronary artery smooth muscle.
Str[stod]obaek, Dorte, Palle Christophersen, Steen Dissing &
S[stod]oren-Peter Olesen.
NeuroSearch A/S, 26B Smedeland, DK-2600 Glostrup, Denmark;
Department of Medical Physiology, University of Copenhagen,
Denmark
APStracts 3:0196C, 1996.
Coronary artery smooth muscle cells express G protein-coupled
purinoceptors, and we report here for the first time how receptor
activation by extracellular ATP influences cell membrane currents and
membrane potential in human cells. ATP (100 [mu]M) stimulated a
triphasic change in membrane potential lasting several seconds, which
was caused by sequential opening of transient inward and outward
conductances. The inward current was carried by Cl- and the outward
current by K+, as shown by ion substitution and changes in holding
potential. Both currents were independent of the presence of external
Ca2+, but were blocked by strong buffering of Ca2+ in the internal
solution. The P2U- and P2Y-purinoceptor agonists uridine-5'
-triphosphate and 2-methylthioadenosine-5'-triphosphate activated
similar currents, whereas the P2X- receptor agonist [alpha],[beta]
-methyleneadenosine-5'-triphosphate and the P1-receptor agonist
adenosine failed to stimulate any whole-cell currents. The ATP
-activated K+ current was inhibited by iberiotoxin (200 nM), and it
was potentiated by the BK channel activator NS 1619 (30 [mu]M). In
cell-attached recordings, ATP activated a 230 pS BK channel. In
conclusion, ATP acting via P2-purinoceptors stimulated release of
Ca2+ from internal stores and transiently activated depolarizing Cl-
and hyperpolarizing BK channels in human coronary artery smooth
muscle cells.
Received 3 January 1996; accepted in final form 20 May 1996.
APS Manuscript Number C5-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 July 96