ETHANOL MODULATES CALMODULIN-DEPENDENT CA2-ACTIVATED ATPASE IN SYNAPTIC PLASMA-MEMBRANES()

The effects of ethanol in vitro on calmodulin-dependent Ca2+-activated ATPase (CaM-Ca2+-ATPase) activity were studied in synaptic plasma mem branes (SPM) prepared from the brain of normal and chronically ethanol -treated rats. In SPM from normal animals, ethanol at 50-200 mM inhibi ted the Ca2+-ATPase activity. Lineweaver-Burk analysis indicates that the inhibition was the result of a decreased affinity of the enzyme fo r calmodulin, whereas the maximum activity of the enzyme was not chang ed. Arrhenius analysis indicates that the enzyme activity was influenc ed by lipid transition of the membranes, and ethanol in vitro resulted in a shift of the transition temperature toward a lower value. From a nimals receiving chronic ethanol treatment (3 weeks), the SPM were res istant to the inhibitory effect of ethanol on the enzyme activity. The resistance to ethanol inhibition was correlated with a higher enzyme affinity for calmodulin and a higher transition temperature, as compar ed with normal SPM. Since the calmodulin-dependent Ca2+-ATPase in syna ptic plasma membranes is believed to be the Ca2+ pump controlling free Ca2+ levels in synaptic terminals, its inhibition by ethanol could th erefore lead to altered synaptic activity.