Ethanol sensitivity of BKCa channels from arterial smooth muscle does not require the presence of the β1-subunit

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Ethanol inhibition of largeconductance, 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 (β) 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 β1-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 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 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 β1-subunits, which determines channel sensitivity to dihydrosoyaponin-I and 17β-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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume284
Issue number6 53-6
StatePublished - Jun 1 2003

Fingerprint

Smooth Muscle
Muscle
Ethanol
Muscle Cells
Alcohols
Calcium-Activated Potassium Channels
Muscle Contraction
Xenopus
Oocytes
Estradiol
Modulation
Tissue
Membranes
Lipids
Electric potential

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology

Cite this

@article{c39ea0a3a9be46c1a19082962c4e1e87,
title = "Ethanol sensitivity of BKCa channels from arterial smooth muscle does not require the presence of the β1-subunit",
abstract = "Ethanol inhibition of largeconductance, 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 (β) 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 β1-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 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 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 β1-subunits, which determines channel sensitivity to dihydrosoyaponin-I and 17β-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.",
author = "Alejandro Dopico",
year = "2003",
month = "6",
day = "1",
language = "English (US)",
volume = "284",
journal = "American Journal of Physiology",
issn = "0363-6143",
publisher = "American Physiological Society",
number = "6 53-6",

}

TY - JOUR

T1 - Ethanol sensitivity of BKCa channels from arterial smooth muscle does not require the presence of the β1-subunit

AU - Dopico, Alejandro

PY - 2003/6/1

Y1 - 2003/6/1

N2 - Ethanol inhibition of largeconductance, 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 (β) 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 β1-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 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 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 β1-subunits, which determines channel sensitivity to dihydrosoyaponin-I and 17β-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.

AB - Ethanol inhibition of largeconductance, 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 (β) 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 β1-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 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 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 β1-subunits, which determines channel sensitivity to dihydrosoyaponin-I and 17β-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.

UR - http://www.scopus.com/inward/record.url?scp=0038273863&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038273863&partnerID=8YFLogxK

M3 - Article

C2 - 12570985

AN - SCOPUS:0038273863

VL - 284

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6143

IS - 6 53-6

ER -