Further characterization of the effect of ethanol on voltage-gated Ca2+ channel function in developing CA3 hippocampal pyramidal neurons

• Acute ethanol reduces somatic and dendritic Ca2+ transients in CA3 pyramidal neurons.
• Ca2+ channel function is not altered during withdrawal from repeated ethanol exposures.
• The contribution of L-type voltage-gated Ca2+ channels is not altered during withdrawal periods.

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 Ca2+ channels (Zucca and Valenzuela, 2010). We found evidence indicating that voltage-gated Ca2+ 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 Ca2+ channels in CA3 pyramidal neurons using Ca2+ imaging techniques. These experiments revealed that acute ethanol exposure inhibits voltage-gated Ca2+ channels both in somatic and proximal dendritic compartments. To investigate the long-term consequences of ethanol on voltage-gated Ca2+ channels, we used patch-clamp electrophysiological techniques to assess the function of L-type voltage-gated Ca2+ 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 3rd trimester-equivalent ethanol exposure transiently inhibits L-type voltage-gated Ca2+ 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.