ETHANOL MODULATES [I-125] CALMODULIN-BINDING TO SYNAPTIC PLASMA-MEMBRANES FROM RAT-BRAIN

The effects of ethanol in vitro on Ca++-dependent binding of [I-125] c almodulin to brain synaptic plasma membranes (SPM) from control and ch ronically ethanol-treated rats were studied, in SPM from control anima ls, ethanol at 50 to 200 mM inhibited [I-125] calmodulin binding; the inhibition was correlated with a decreased membrane affinity for [I-12 5]calmodulin as shown by Scatchard analysis, and an increased dissocia tion of [I-125]calmodulin-membrane complexes as shown by kinetic analy sis. Arrhenius analysis indicates that [I-125]calmodulin binding was i nfluenced by lipid transition of the membrane, and that ethanol in vit ro resulted in a shift of the transition temperature toward a lower va lue. From animals receiving chronic ethanol treatment (3 weeks), the S PM were found to be resistant to the inhibitory effect of ethanol on b inding, The resistance to ethanol inhibition was correlated with a hig her membrane affinity for [I-125]calmodulin and a higher transition te mperature, as compared with control SPM. Because a variety of membrane -bound processes are regulated by calmodulin or calmodulin-dependent p rocesses, the inhibitory effect of ethanol on membrane binding of calm odulin could lead to a cascade of consequences in synaptic function. M oreover, the resistance of the membranes to ethanol inhibition after c hronic ethanol treatment implies that membrane binding of calmodulin i s part of the mechanism underlying alcohol tolerance and dependence.