VOLTAGE-JUMP RELAXATION KINETICS FOR WILD-TYPE AND CHIMERIC BETA-SUBUNITS OF NEURONAL NICOTINIC RECEPTORS

We have studied the voltage-jump relaxation currents for a series of n euronal nicotinic acetylcholine receptors resulting from the coexpress ion of wild-type and chimeric beta 4/beta 2 subunits with alpha 3 subu nits in Xenopus oocytes. With acetylcholine as the agonist, tile wild- type alpha 3 beta 4 receptors displayed five- to eightfold slower volt age-jump relaxations than did the wild-type alpha 3 beta 2 receptors. In both cases, the relaxations could best be described by two exponent ial components of approximately equal amplitudes over a wide range of [ACh]'s. Relaxation rate constants increased with [ACh] and saturated at 20- to 30-fold lower concentrations for the alpha 3 beta 2 receptor than for the alpha 3 beta 4 receptor, as observed previously for the peak steady state conductance. Furthermore, the chimeric beta 4/beta 2 subunits showed a transition in the concentration dependence of the r ate constants in the region between residues 94 and 109, analogous to our previous observation with steady state conductances. However, our experiments with a series of beta-subunit chimeras did not localize re sidues that govern the absolute value of the kinetic parameters. Hill coefficients for the relaxations also differed from those previously m easured for steady state responses. The data reinforce previous conclu sions that the region between residues 94 and 109 on the beta subunit plays a role in binding agonist but also show that other regions of th e receptor control gating kinetics subsequent to the binding step.