一个新发现的蛋白质靶标可能有助于调节小鼠的酒精耐受效应，而且可能有助于确定一个动物是否容易酗酒。酒精耐受是酒精成瘾的一个关键方面，它被认为影响着谁将变得对酒精成瘾，而谁不会成瘾。
Gilles Martin及其同事发现了一种蛋白质的一个亚基——这个被称为BK通道蛋白的蛋白质此前被认为和酒精耐受有联系——并证明了清除这个亚基可能会让急性酒精耐受以及它在动物身上表现出的行为效应加速出现。这组科学家把生长在培养基中的细胞的β4蛋白亚基去除，结果发现受影响的神经元在接触到酒精之后的数分钟就显示出了快速耐受性。对照组的小鼠在重复摄入酒精之后显示出了运动显著减少，而试验组的小鼠显示出迅速恢复了正常运动。这组科学家证明了当允许两组小鼠自由地获取酒精的时候，敲除该亚基的小鼠摄入的酒精显著多于对照组小鼠。这组作者提出，β4亚基在分子、细胞和行为水平上控制着酒精的急性耐受，而且它可能为发现成瘾风险最大的人和治疗酒精成瘾提供一个治疗靶标。（生物谷Bioon.com）
生物谷推荐原始出处：
PNAS published ahead of print November 3, 2008, doi:10.1073/pnas.0801068105
Identification of a BK channel auxiliary protein controlling molecular and behavioral tolerance to alcohol
Gilles E. Martin, Linzy M. Hendrickson, Krista L. Penta, Ryan M. Friesen, Andrzej Z. Pietrzykowski, Andrew R. Tapper, and Steven N. Treistman
Tolerance, described as the loss of drug effectiveness over time, is an important component of addiction. The degree of acute behavioral tolerance to alcohol exhibited by a na?ve subject can predict the likelihood of alcohol abuse. Thus, the determinants of acute tolerance are important to understand. Calcium- and voltage-gated (BK) potassium channels, consisting of pore forming α and modulatory β subunits, are targets of ethanol (EtOH) action. Here, we examine the role, at the molecular, cellular, and behavioral levels, of the BK β4 subunit in acute tolerance. Single channel recordings in HEK-293 cells show that, in the absence of β4, EtOH potentiation of activity exhibits acute tolerance, which is blocked by coexpressing the β4 subunit. BK channels in acutely isolated medium spiny neurons from WT mice (in which the β4 subunit is well-represented) exhibit little tolerance. In contrast, neuronal BK channels from β4 knockout (KO) mice do display acute tolerance. Brain slice recordings showed tolerance to EtOH's effects on spike patterning in KO but not in WT mice. In addition, β4 KO mice develop rapid tolerance to EtOH's locomotor effects, whereas WT mice do not. Finally, in a restricted access ethanol self-administration assay, β4 KO mice drink more than their WT counterparts. Taken together, these data indicate that the β4 subunit controls ethanol tolerance at the molecular, cellular, and behavioral levels, and could determine individual differences in alcohol abuse and alcoholism, as well as represent a therapeutic target for alcoholism.
