A comparison of current‐voltage relations for full and partial agonists.

Abstract

Local conductance changes produced by various bath-applied agonists at frog [Rana pipiens] end-plate membrane were measured using focal recording of extracellular potential in voltage-clamped muscle fibers. The potential difference between a focal micropipette placed on the nerve terminal and another micro-pipette placed on or near inactive membrane was taken as proportional to the agonist-induced current through a small patch of end-plate membrane. During application of sufficiently low concentrations of full agonists (carbachol, ACh [acetylcholine]) and partial agonists (choline and decamethonium) the I-V [current-voltage] relation of end-plate membrane showed strong curvature in the range of -60 to -130 mV. The slope of I-V relations increased exponentially with membrane hyperpolarization, an e[base for natural logarithms]-fold change in conductance occurring for about 50 mV potential shift. The curvature of the I-V relation of end-plate-membrane activated by the partial agonists choline and decamethonium became less as the agonist concentration was increased, and with high concentrations (choline 15 mM; decamethonium 250 .mu.M) the I-V relation became almost straight. When end-plate currents produced by high concentrations of partial agonists were matched by application of equi-active concentrations of carbachol, the carbachol-activated membrane still showed as much curvature in its I-V relation as when low concentrations of carbachol were used. Choline and decamethonium concentrations, for which the I-V relation was straight, produced much greater depression of miniature end-plate currents than did carbachol concentrations which produced the same membrane current at the holding potential. I-V relations for full agonists at high concentrations were obtained after .alpha.-bungarotoxin pre-treatment. During application of carbachol (400-500 .mu.M) and ACh (30-40 .mu.M; after complete inhibition of acetylcholinesterase activity) the I-V relation of end-plate membrane is much less curved than during application of low concentrations. Apparently either the voltage sensitivity of agonist-induced end-plate conductance reflects voltage sensitivity of agonist binding, or the partial agonists used can exert a voltage-dependent local anesthetic action in addition to their agonist activity.