Crews F T, Morrow A L, Criswell H, Breese G
Center for Alcohol Studies, School of Medicine, University of North Carolina at Chapel Hill 27599, USA.
Int Rev Neurobiol. 1996;39:283-367. doi: 10.1016/s0074-7742(08)60670-4.
Ion channels play critical roles in nervous system function, from initiating rapid synaptic activity to propagation of action potentials. Studies have indicated that many of the effects of ethanol on the nervous system are likely caused by the actions of ethanol on ion channels. Ion channels are multimeric structures that gate ions through subtle changes in tertiary structure. Ethanol readily enters molecular sites within multimeric ion channels, modifying intermolecular forces and bonds that are important for the open-close-inactivation kinetic properties of channels. The diversity of channel composition caused by the multimeric structure results in subtypes of channels that have a spectrum of sensitivity to ethanol that translates into brain regional differences in ethanol sensitivity, in part caused by differences in ion channel subunit composition. Ethanol has been shown to affect both receptor-activated ion channels and voltage-gated ion channels. The acute intoxicating and incoordinating effects of ethanol are probably related to inhibition of subtypes of NMDA-glutamate receptor ion channels and potentiation of certain subtypes of GABAA receptor ion channels. Effects on these channels, as well as glycine, nicotinic cholinergic, serotonergic, and other ion channels, likely contribute to the euphoric, sedative, and other acute actions of ethanol. Changes in ion channel subunit composition, density, and properties probably also contribute to ethanol tolerance, dependence, withdrawal hyperexcitability, and neurotoxicity. A substantial number of studies have implicated glutamate NMDA receptor, GABAA, and L-type voltage-gated calcium channels in the adaptive changes in the brain during chronic ethanol exposure. The diversity of ion channels subunits, their prominent role in brain function, and ethanol action are likely to make them important contributors to alcoholism and alcohol abuse.
离子通道在神经系统功能中发挥着关键作用，从启动快速突触活动到动作电位的传播。研究表明，乙醇对神经系统的许多影响可能是由乙醇对离子通道的作用引起的。离子通道是多聚体结构，通过三级结构的细微变化来控制离子通过。乙醇很容易进入多聚体离子通道内的分子位点，改变对通道的开闭 - 失活动力学特性很重要的分子间力和键。多聚体结构导致的通道组成多样性产生了对乙醇敏感性不同的通道亚型，这转化为大脑区域对乙醇敏感性的差异，部分原因是离子通道亚基组成的差异。已表明乙醇会影响受体激活的离子通道和电压门控离子通道。乙醇的急性中毒和不协调作用可能与抑制NMDA - 谷氨酸受体离子通道的亚型以及增强某些GABAA受体离子通道的亚型有关。对这些通道以及甘氨酸、烟碱型胆碱能、5 - 羟色胺能和其他离子通道的影响，可能有助于乙醇的欣快、镇静和其他急性作用。离子通道亚基组成、密度和特性的变化可能也有助于乙醇耐受性、依赖性、戒断性过度兴奋和神经毒性。大量研究表明，谷氨酸NMDA受体、GABAA和L型电压门控钙通道参与了慢性乙醇暴露期间大脑的适应性变化。离子通道亚基的多样性、它们在脑功能中的突出作用以及乙醇的作用，可能使它们成为酗酒和酒精滥用的重要因素。
