title: Further characterization of the effect of ethanol on voltage-gated Ca(2+) channel function in developing CA3 hippocampal pyramidal neurons.
abstract: Developmental ethanol exposure damages the hippocampus, a brain region involved in learning and memory. Alterations in synaptic transmission and plasticity may play a role in this effect of ethanol. We previously reported that acute and repeated exposure to ethanol during the third trimester-equivalent inhibits long-term potentiation of GABAA receptor-dependent synaptic currents in CA3 pyramidal neurons through a mechanism that depends on retrograde release of brain-derived neurotrophic factor driven by activation of voltage-gated Ca(2+) channels (Zucca and Valenzuela, 2010). We found evidence indicating that voltage-gated Ca(2+) channels are inhibited in the presence of ethanol, an effect that may play a role in its mechanism of action. Here, we further investigated the acute effect of ethanol on the function of voltage-gated Ca(2+) channels in CA3 pyramidal neurons using Ca(2+) imaging techniques. These experiments revealed that acute ethanol exposure inhibits voltage-gated Ca(2+) channels both in somatic and proximal dendritic compartments. To investigate the long-term consequences of ethanol on voltage-gated Ca(2+) channels, we used patch-clamp electrophysiological techniques to assess the function of L-type voltage-gated Ca(2+) channels during and following ten days of vapor ethanol exposure. During ethanol withdrawal periods, the function of these channels was not significantly affected by vapor chamber exposure. Taken together with our previous findings, our results suggest that 3(rd) trimester-equivalent ethanol exposure transiently inhibits L-type voltage-gated Ca(2+) channel function in CA3 pyramidal neurons and that compensatory mechanisms restore their function during ethanol withdrawal. Transient inhibition of these channels by ethanol may be, in part, responsible for the hippocampal abnormalities associated with developmental exposure to this agent.
authors.affiliation: Department of Neurosciences, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
authors.forename: Russell A
authors.initials: RA
authors.lastname: Morton
authors.affiliation: Department of Neurosciences, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA. Electronic address: fvalenzuela@salud.unm.edu.
authors.forename: C Fernando
authors.initials: CF
authors.lastname: Valenzuela
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D056654:CA3 Region, Hippocampal / Q000187:drug effects*; D015220:Calcium Channels / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000633:toxicity*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017966:Pyramidal Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D015220:Calcium Channels; D002492:Central Nervous System Depressants; D000431:Ethanol
keywords: Calcium; Hippocampus; Neonatal; Third trimester; Vapor chamber; Voltage-gated channel