Am J Physiol Cell Physiol 2003 Jun 01;2846:C1468-80. doi: 10.1152/ajpcell.00421.2002.

Ethanol sensitivity of BK(Ca) channels from arterial smooth muscle does not require the presence of the beta 1-subunit.

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Ethanol inhibition of large-conductance, Ca(2+)-activated K(+) (BK(Ca)) channels in aortic myocytes may contribute to the direct contraction of aortic smooth muscle produced by acute alcohol exposure. In this tissue, BK(Ca) channels consist of pore-forming (bslo) and modulatory (beta) subunits. Here, modulation of aortic myocyte BK(Ca) channels by acute alcohol was explored by expressing bslo subunits in Xenopus oocytes, in the absence and presence of beta(1)-subunits, and studying channel responses to clinically relevant concentrations of ethanol in excised membrane patches. Overall, average values of bslo channel activity (NP(o), with N = no. of channels present in the patch; P(o) = probability of a single channel being open) in response to ethanol (3-200 mM) mildly decrease when compared with pre-ethanol, 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 NP(o) is observed. In this subset, the maximal effect is obtained with 100 mM ethanol, at which NP(o) reaches 46.2 +/- 9% of control. The presence of beta(1)-subunits, which determines channel sensitivity to dihydrosoyaponin-I and 17beta-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 Ca(2+) 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 BK(Ca) channel activity.

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Species referenced: Xenopus laevis