Comparison with Reversibly Bound Agonists at Electrophorus Electrop laques

ABSTRACT After disulphide bonds are reduced with dithiothreitol, trans-3-(a-bromomethyl)-3'- [a- (t rimethylammonium) ethyl]azobenzene (trans-QBr) alkylates a sulfhydryl group on receptors. The membrane conductance induced by this "tethered agonist " shares many properties with that induced by reversible agonists. Equilibrium conductance increases as the membrane potential is made more negative; the voltage sensitivity resembles that seen with 50 btM carbachol. Voltage-jump relaxations follow an exponential time-course; the rate constants are about twice as large as those seen with 50 #M carbachol and have the same voltage and temperature s nsitivity. With reversible agonists, the rate of channel opening increases with the frequency of agonist-receptor collisions: with tethered trans-QBr, this rate depends only on intramolecular events. In comparison to the conductance induced by reversible agonists, the QBr-induced conductance is at least 10-fold less sensitive to competitive blockade by tubocurarine and roughly as sensitive to "open-channel blockade " by QX-222. Light-flash experiments with tethered QBr resemble those with the reversible photoisomerizable agonist