Review Regulation of neuronal voltage-gated calcium channels by ethanol p Helen J. Walter, Robert O. Messing* (Graduate Programs in Biological Sciences and Neuroscience), Ernest Gallo Clinic & Research Center, Department of Neurology, University of California, San Francisco, CA 94110, USA Received 16 March 1999; accepted 16 March 1999 Abstract Voltage-gated calcium channels are key regulators of neuronal excitability. Several studies indicate that intoxicating concentrations of ethanol inhibit L-type, N-type and possibly T-type channels. The eects of ethanol on other channel subtypes are not yet clear. Chronic exposure to ethanol is associated with increases in functional L-type channels and this may contribute to signs of ethanol withdrawal. Preclinical studies in animals suggest that L-type calcium channel antagonists decrease ethanol consumption and signs of alcohol withdrawal. Although L-type channel antagonists do not appear to alter the performance impairing or psychological eects of acute ethanol administration, clinical trials will be needed to determine if L-type channel antagonists reduce ethanol consumption in humans. # 1999 Elsevier Science Ltd. All rights reserved. Contents 1. Introduction ........................................................... 95 2. Classi®cation, structure and pharmacology of VGCCs ............................. 97 3. L-type channels ......................................................... 97 4. Non-L-type VGCCs ..................................................... 98 5. Conclusions ........................................................... 99 References ................................................................. 99 1. Introduction Alcoholism is a major public health problem and in the United States the economic cost of alcohol abuse due to medical care, lost employment, premature death, alcohol-related crime, property damage and ad- ministration of social welfare has been estimated to be at least $70 billion per year (Shalala, 1993). Despite the high cost to society, pharmacological options for treatment of alcoholism are few. There is hope that new therapies may arise from understanding the bio- chemical mechanisms involved in alcohol intoxication, tolerance and dependence. Research over the past two decades has identi®ed voltage-gated Ca 2+ channels (VGGCs) as major contributors to alcohol's eects on neural function and on behavioral responses to alco- Neurochemistry International 35 (1999) 95±101 0197-0186/99/$ - see front matter # 1999 Elsevier Science Ltd. All rights reserved. PII: S0197-0186(99)00050-9 p This work is supported by grants from the Public Health Service and the Alcoholic Beverage Medical Research Foundation to R.O.M. * Corresponding author. Building 1, Room 101, 1001 Potrero Avenue, San Francisco, CA 94110, USA. Tel.: +1-415-648-7111 ext. 329; fax: +1-415-648-7116. E-mail address: romes@itsa.ucsf.edu (R.O. Messing)