Effects of chronic alcohol administration on synaptic membrane Na+-Ca2+ exchange activity.

We have recently reported that ethanol and other n-alkanols added to in vitro assays inhibit the activity of the Na+-Ca2+ exchange system in brain synaptic plasma membrane vesicles. The present studies were undertaken to determine whether in vivo chronic ethanol administration leads to alterations in this Na+-Ca2+ antiporter that might be indicative of an adaptive response to alcohol. The Na+-dependent Ca2+ transport activity in the plasma-membrane fractions obtained was measured at various Ca2+ concentrations. Results of these experiments revealed that a 3-week ethanol regimen brought about a significant increase in the Na+-dependent Ca2+ transport activity only in the membrane fraction enriched in synaptic junctional complexes. These membranes showed a near doubling in the maximal transport activity of the antiporter in alcohol-treated compared with the control animals. Changes in the kinetic parameters were reversible as the Na+-Ca2+ exchange activity in these membranes from animals maintained on alcohol for 3 weeks and then withdrawn for 1 week was indistinguishable from that of membranes from control animals. Thus it appears that ethanol-treated animals make a reversible adaptation in their neuronal cell membranes to compensate for the acute effects of ethanol on the Na+-Ca2+ antiporter.