title: K(Ca)2 channels: novel therapeutic targets for treating alcohol withdrawal and escalation of alcohol consumption.
abstract: Small-conductance, calcium-activated potassium (K(Ca)2) channels influence neuronal firing properties, intrinsic excitability, and NMDA receptor-dependent synaptic responses and plasticity. In this mini-review, we discuss new evidence that chronic alcohol-associated plasticity critically involves K(Ca)2 channels in hippocampus, ventral tegmental area, and nucleus accumbens. K(Ca)2 channel activity can modulate the magnitude of excitation of midbrain dopamine neurons induced by acute alcohol exposure. Emerging evidence indicates that K(Ca)2 channels regulate neuroadaptations to chronic alcohol that contribute to withdrawal hyperexcitability and escalation of voluntary alcohol consumption. Restoring K(Ca)2 channel activity can attenuate the severity of the alcohol withdrawal syndrome in vivo and withdrawal-associated neurotoxicity in vitro. Pharmacological modulation of K(Ca)2 channels can bi-directionally influence drinking behavior in rat and mouse models of voluntary alcohol consumption. Collectively, these studies using various rodent models have clearly indicated a central role for K(Ca)2 channels in the neuroplasticity of chronic alcohol exposure. In addition, accumulating evidence suggests that K(Ca)2 channels are a novel therapeutic target to alleviate the symptoms of alcohol withdrawal and reduce high amounts of alcohol drinking.
authors.affiliation: Medical University of South Carolina, Departments of Neurosciences and Psychiatry & Behavioral Sciences, Charleston, SC 29425, USA. mulholl@musc.edu
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Mulholland
mesh_terms: D000428:Alcohol Drinking / Q000378:metabolism; D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D000431:Ethanol / Q000494:pharmacology*; D051379:Mice; D009473:Neuronal Plasticity / Q000187:drug effects*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
chemical_list: D051640:Small-Conductance Calcium-Activated Potassium Channels; D000431:Ethanol