Li C, Aguayo L, Peoples R W, Weight F F
Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892.
Mol Pharmacol. 1993 Oct;44(4):871-5.
The cellular mechanisms by which ethanol affects nervous system function are poorly understood. However, evidence has been accumulating that ethanol can affect the function of neurotransmitter-gated ion channels. Extracellular ATP has recently been reported to produce excitatory actions in the peripheral and central nervous systems by activating ligand-gated ion channels. We studied the effect of ethanol on membrane ion current activated by extracellular ATP in isolated bullfrog dorsal root ganglion neurons, by means of the whole-cell patch-clamp technique. The amplitude of the ATP-activated current was decreased by ethanol in a concentration-dependent manner over the range of 3-500 mM. The average inhibition of 1 microM ATP-activated current by 100 mM ethanol was 64 +/- 3%, and the concentration of ethanol that produced 50% inhibition was 68 mM. Ethanol inhibition of ATP-activated current was not dependent on membrane potential from -80 to +40 mV, and ethanol did not change the reversal potential of ATP-activated current. Ethanol (100 or 400 mM) shifted the ATP concentration-response curve to the right, increasing the EC50 for ATP from 3.0 microM to 6.0 microM or 22.3 microM, respectively, but did not reduce the maximal response to ATP. The results suggest that ethanol inhibits ATP-activated current by increasing the apparent dissociation constant for the ATP receptor.
乙醇影响神经系统功能的细胞机制目前还知之甚少。然而，越来越多的证据表明乙醇能够影响神经递质门控离子通道的功能。最近有报道称，细胞外ATP通过激活配体门控离子通道，在周围和中枢神经系统中产生兴奋作用。我们运用全细胞膜片钳技术，研究了乙醇对分离的牛蛙背根神经节神经元中由细胞外ATP激活的膜离子电流的影响。在3 - 500 mM的浓度范围内，乙醇以浓度依赖的方式降低了ATP激活电流的幅度。100 mM乙醇对1 microM ATP激活电流的平均抑制率为64±3%，产生50%抑制作用的乙醇浓度为68 mM。乙醇对ATP激活电流的抑制作用不依赖于 - 80至 + 40 mV的膜电位，且乙醇不会改变ATP激活电流的反转电位。乙醇（100或400 mM）使ATP浓度 - 反应曲线右移，将ATP的半数有效浓度（EC50）分别从3.0 microM增加到6.0 microM或22.3 microM，但并未降低对ATP的最大反应。结果表明，乙醇通过增加ATP受体的表观解离常数来抑制ATP激活电流。
