Ethanol sensitivity of BK(Ca) channels from arterial smooth muscle does not require the presence of the beta 1-subunit.
Ethanol sensitivity of BK(Ca) channels from arterial smooth muscle does not require the presence of the beta 1-subunit.
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发表时间：
2003
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通讯作者：
A. Dopico
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作者：
A. Dopico
乙醇对主动脉肌细胞大电导钙激活钾通道（BK（Ca））的抑制作用可能与急性乙醇暴露引起的主动脉平滑肌直接收缩有关。在该组织中，BK（Ca）通道由成孔（bK）和调节（β）亚基组成。在这里，调制的主动脉肌细胞BK（Ca）通道急性酒精进行了探讨，通过表达在非洲爪蟾卵母细胞中，在β（1）-亚基的存在和不存在，并研究在切除的膜补丁的临床相关浓度的乙醇的通道响应。总的来说，当与乙醇前等渗对照相比时，响应于乙醇（3-200 mM）的bcl 2通道活性的平均值（NP（o），其中N =贴片中存在的通道的数量; P（o）=单个通道打开的概率）轻度降低。然而，通道响应在所有乙醇浓度下均表现出定性异质性。在大多数贴剂中（42/71贴剂，即，59%），观察到NP（o）的可逆减少。在该亚组中，使用100 mM乙醇获得最大效果，此时NP（o）达到对照的46.2 +/-9%。决定通道对二氢大豆皂苷-I和17 β-雌二醇敏感性的β（1）-亚基的存在不能改变乙醇对β-雌二醇通道的作用。乙醇抑制bmos通道的结果，从一个显着增加的平均关闭时间。虽然门控的电压依赖性不受影响，但乙醇降低了Ca（2+）门控通道的表观有效性。这些变化发生时不改变通道传导。总之，一个新的分子机制，可能有助于乙醇诱导的主动脉平滑肌收缩已被确定和表征：乙醇和bkB亚基和/或其脂质微环境之间的功能相互作用，这导致BK（Ca）通道活性降低。
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.