TETRAETHYLAMMONIUM - VOLTAGE-DEPENDENT ACTION ON ENDPLATE CONDUCTANCE AND INHIBITION OF LIGAND-BINDING TO POSTSYNAPTIC PROTEINS

Tetraethylammonium (Et4N+) ions depressed the amplitude and accelerated the decay rate of spontaneously occurring and nerve-evoked endplate currents (EPCs) in frog sartorius muscle. The relationship between peak EPC amplitude and membrane potential became nonlinear in the presence of 100 μM Et4N+, and with drug concentrations of 250 μM or greater the current-voltage relationship exhibited negative conductance in the hyperpolarized region. Et4N+ modified the exponential dependence of the EPC decay on membrane potential such that the decays between -150 and -50 mV were abbreviated and voltage independent but remained near control levels at more positive membrane potentials. The minimal effective concentration of Et4N+ for altering the EPC time course was 10, and maximal effects were attained with 100 μM. Little additional shortening in the EPC decay phase was detected on raising the drug concentration to 1000 μM. Acetylcholine noise analysis revealed a voltage-dependent reduction in the mean channel open time, which was comparable in magnitude to the shortening in the EPC decay, and a depression of single-channel conductance. In concomitant biochemical studies, Et4N+ was found to inhibit the binding of both [3H]acetylcholine and [3H]perhydrohistrionicotoxin to receptor-rich membranes from the electric organ of Torpedo ocellata with K(i) values of 200 μM and 280 μM, respectively. These results suggest that Et4N+ interacts with both the acetylcholine receptor and its associated ionic channel. The voltage-dependent actions of Et4N+ are attributed to blockade of the ionic channel in closed as well as open conformation.