Rates and equilibria a t the acetylcholine receptor of Electrophorus electroplaques: a study of neurally evoked postsyn- aptic currents and of voltage-jump relaxations

ABSTRACT Kinetic measurements are employed to reconstruct he steady-state activation of acetylcholine {ACh] receptor channels in Electrophorus electroplaques. Neurally evoked postsynaptic currents (PSCs) decay exponentially; at 15°C the rate constant, ct. equals 1.2 ms-t at 0 mV and decreases e-fold for every 86 mV as the membrane voltage is made more negative. Voltage=jump relaxations have been measured with bath-applied ACh, decamethonium, carbachol, or suberyldicholine. We interpret he reciprocal relaxation time I/T as the sum of the rate constant ~ for channel closing and a first-order rate constant for channel opening. Where measurable, the opening rate increases linearly with lagonist] and does not vary with voltage. The voltage sensitivity of small steady-state conductances (e-fold for 86 mV) equals that of the closing rate ~x, confirming that the opening rate has little or no additional voltage sensitivity. Exposure to ~x-bungarotoxin irreversibly decreases the agonist-induced conductance hut does not affect the relaxation kinetics. Tubocurar ine reversibly reduces both the conductance and the opening rate. In the simultaneous presence of two agonist species, voltage-jump relaxations have at least two exponential components. The data are fit by a model in which (a) the channel opens as the~receptor binds the second in a sequence of two agonist molecules, with a forward rate constant o l0 T to 2 × l0 s M-t s-l; and (b) the channel then closes as either agonist molecule dissociates, with a voltage-dependent rate constant of 102 to 3 × 103 s-1