Ethanol sensitivity of BKCa channels cloned from arterial smooth muscle does not
require the ß1-subunit.
Dopico, Alejandro M.
Department of Pharmacology and Program in Neuroscience, University of Tennessee
Health Science Center, Memphis, Tennessee 38163
APStracts 10:0067C, 2003.
Ethanol inhibition of Ca2+-activated K+ (BKCa) channels in aortic myocytes may
contribute to the direct contraction of aortic smooth muscle produced by acute alcohol
exposure. In this tissue, BKCa channels consist of pore-forming (bslo) and modulatory
(ß) subunits. Here, modulation of aortic myocyte BKCa channels by acute alcohol was
explored by expressing bslo subunits in Xenopus oocytes, in the absence and presence of
ß1-subunits, and studying channel responses to clinically relevant concentrations of
ethanol in excised membrane patches. Overall, average values of bslo channel activity
(NPo, with N = no. of channels present in the patch; Po = probability of a single channel
being open) in response to ethanol (3-200 mM) mildly decrease when compared with
preethanol, isosmotic controls. However, channel responses show qualitative
heterogeneity at all ethanol concentrations. In the majority of patches (42/71 patches, i.e.,
59%), a reversible reduction in NPo is observed. In this subset, the maximal effect is
obtained with 100 mM ethanol, at which NPo reaches 46.2 ± 9% of control. The presence
of ß1-subunits, which determines channel sensitivity to dihydrosoyaponin-I and 17ß-
estradiol, fails to modify ethanol action on bslo channels. Ethanol inhibition of bslo
channels results from a marked increase in the mean closed time. Although the voltage
dependence of gating remains unaffected, the apparent effectiveness of Ca2+ to gate the
channel is decreased by ethanol. These changes occur without modifications of channel
conduction. In conclusion, a new molecular mechanism that may contribute to ethanol-
induced aortic smooth muscle contraction has been identified and characterized: a
functional interaction between ethanol and the bslo subunit and/or its lipid
microenvironment, which leads to a decrease in BKCa channel activity.
Received 13 September 2002; accepted in final form 30 January 2003
APS Manuscript Number C421-2.
Article publication pending Am J Physiol Cell Physiol
ISSN 1080-4757 Copyright 2003 The American Physiological Society.
Published in APStracts on 25 March 2003