人喝醉后,，通常感覺暈頭轉(zhuǎn)向,，大腦好像不轉(zhuǎn)了一樣，但對于大腦為什么會出現(xiàn)這樣的反應(yīng)卻不清楚,。美國一項(xiàng)最新研究就查明了醉酒過程中大腦活動的具體分子機(jī)制,。研究成人員稱這將有助于開發(fā)針對酒精中毒、藥物上癮甚至癲癇癥的新型療法,。
美國索爾克生物研究所科研人員在新一期《自然·神經(jīng)科學(xué)》雜志上報告說,，酒精成分即乙醇，被認(rèn)為會改變大腦內(nèi)神經(jīng)細(xì)胞之間的信號傳遞,。此前一些研究認(rèn)為,，乙醇會直接與離子通道蛋白質(zhì)相互作用，但到目前都沒有查明相互作用的具體位置,。
索爾克生物研究所最新的研究發(fā)現(xiàn),，乙醇與大腦中一種鉀離子通道蛋白質(zhì)內(nèi)的某個特定位置相互作用。醫(yī)學(xué)研究已知,，這種名為GIRK的鉀離子通道在藥物濫用和癲癇發(fā)作時的大腦活動中扮演關(guān)鍵角色,。
最新的實(shí)驗(yàn)就發(fā)現(xiàn)，乙醇與蛋白質(zhì)內(nèi)的特定位置結(jié)合后,，這一通道被激活“開啟”,，神經(jīng)細(xì)胞之間的“通信聯(lián)絡(luò)”會被減弱，大腦內(nèi)相當(dāng)于產(chǎn)生了“短路”,。
研究人員說,，查明乙醇激活GIRK通道的具體位置，將有助于開發(fā)治療相關(guān)大腦疾病的新療法,。比如,，可以開發(fā)出一種靶向藥物，使乙醇無法與通道蛋白質(zhì)結(jié)合,，來治療酒精依賴,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Neuroscience 28 June 2009 | doi:10.1038/nn.2358
A discrete alcohol pocket involved in GIRK channel activation
Prafulla Aryal1,2, Hay Dvir3, Senyon Choe2,3 & Paul A Slesinger1,2
Abstract
Ethanol modifies neural activity in the brain by modulating ion channels. Ethanol activates G protein–gated inwardly rectifying K+ channels, but the molecular mechanism is not well understood. Here, we used a crystal structure of a mouse inward rectifier containing a bound alcohol and structure-based mutagenesis to probe a putative alcohol-binding pocket located in the cytoplasmic domains of GIRK channels. Substitutions with bulkier side-chains in the alcohol-binding pocket reduced or eliminated activation by alcohols. By contrast, alcohols inhibited constitutively open channels, such as IRK1 or GIRK2 engineered to strongly bind PIP2. Mutations in the hydrophobic alcohol-binding pocket of these channels had no effect on alcohol-dependent inhibition, suggesting an alternate site is involved in inhibition. Comparison of high-resolution structures of inwardly rectifying K+ channels suggests a model for activation of GIRK channels using this hydrophobic alcohol-binding pocket. These results provide a tool for developing therapeutic compounds that could mitigate the effects of alcohol.
1 Peptide Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California, USA.
2 Graduate Program in Biology, Division of Biology, University of California, San Diego, La Jolla, California, USA.
3 Structural Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California, USA.
