Action and mechanism of ethanol on Ca2+-activated potassium channels

Rewarding effect of ethanol involves activation of dopaminergic neurons in ventral tegmental area. Although ethanol inhibits afterhyperpolarization (AHP) of these neurons and increases their firing frequencies, types of ion channels underlie this effect have not been elucidated yet. AHP is generated by the activation of Ca2+-activated K+ channels: BK (100-200 pS); IK (20-85 pS); SK1-3 (2-20 pS). Among them, IK and SK contribute to AHP. To identify the channels, we have expressed IK, SK1-3 and their chimeras in Xenopus oocytes, and examined the effects of ethanol. IK, but not SK, channels were inhibited by ethanol. Among the chimeric channels between IK and SK1, those with pore domain of IK were inhibited by ethanol whereas those with the pore of SK1 were not. The results indicate that IK inhibition may be involved in ethanol-induced activation of dopaminergic neuron, and its pore domain plays an important role in the inhibition mechanism.