CALCIUM MODULATION OF ACTIVATION AND DESENSITIZATION OF NICOTINIC RECEPTORS FROM MOUSE-BRAIN

The effects of extracellular calcium on functional properties of nicot inic receptors from mouse thalamus were investigated. Previous studies have reported that calcium modulates the function of several neuronal nicotinic receptors. A Rb-86(+) ion efflux assay was developed to mea sure nicotinic receptor function from brain tissue, and data indicate that alpha(4)beta(2) receptors may mediate this response. Using the Rb -86(+) efflux assay, calcium effects on receptor activation, desensiti zation induced by high, activating and low, subactivating concentratio ns of agonist, and recovery from desensitization were examined. Effect s of calcium on the kinetics of ligand binding were also investigated. Calcium modulated receptor activation by increasing the maximal respo nse to nicotine in a concentration-dependent manner, without affecting the EC50 of nicotine. Barium, but not magnesium, mimicked the effects of calcium on receptor activation. The increase in receptor activatio n could not be explained by changes in the ratio of activatable to des ensitized receptors as assessed by the kinetics of ligand binding. Des ensitization following activation was unaffected by calcium. Calcium, barium, and magnesium, however, increased the potency of nicotine for desensitization induced by exposure to low, subactivating concentratio ns of nicotine. Recovery from desensitization was not modulated by cal cium. These data suggest that calcium modulates various functional asp ects of nicotinic receptors from mouse brain and may do so via differe nt mechanisms.