一個(gè)新發(fā)現(xiàn)的蛋白質(zhì)靶標(biāo)可能有助于調(diào)節(jié)小鼠的酒精耐受效應(yīng),，而且可能有助于確定一個(gè)動(dòng)物是否容易酗酒。酒精耐受是酒精成癮的一個(gè)關(guān)鍵方面,，它被認(rèn)為影響著誰(shuí)將變得對(duì)酒精成癮,，而誰(shuí)不會(huì)成癮。
Gilles Martin及其同事發(fā)現(xiàn)了一種蛋白質(zhì)的一個(gè)亞基——這個(gè)被稱(chēng)為BK通道蛋白的蛋白質(zhì)此前被認(rèn)為和酒精耐受有聯(lián)系——并證明了清除這個(gè)亞基可能會(huì)讓急性酒精耐受以及它在動(dòng)物身上表現(xiàn)出的行為效應(yīng)加速出現(xiàn)。這組科學(xué)家把生長(zhǎng)在培養(yǎng)基中的細(xì)胞的β4蛋白亞基去除,，結(jié)果發(fā)現(xiàn)受影響的神經(jīng)元在接觸到酒精之后的數(shù)分鐘就顯示出了快速耐受性,。對(duì)照組的小鼠在重復(fù)攝入酒精之后顯示出了運(yùn)動(dòng)顯著減少，而試驗(yàn)組的小鼠顯示出迅速恢復(fù)了正常運(yùn)動(dòng),。這組科學(xué)家證明了當(dāng)允許兩組小鼠自由地獲取酒精的時(shí)候,，敲除該亞基的小鼠攝入的酒精顯著多于對(duì)照組小鼠。這組作者提出,，β4亞基在分子,、細(xì)胞和行為水平上控制著酒精的急性耐受，而且它可能為發(fā)現(xiàn)成癮風(fēng)險(xiǎn)最大的人和治療酒精成癮提供一個(gè)治療靶標(biāo),。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
