Adams_1978_J.Physiol_283_621

1. Local conductance changes produced by various bath-applied agonists at frog end-plate membrane were measured using focal recording of extracellular potential in voltage-clamped muscle fibres. 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 an end-plate membrane. 2. The current-voltage (I--V) relation of active membrane was obtained directly by increasing the membrane potential in a ramp fashion. The change in membrane potential was slow enough for post-synaptic gating processes to reach equilibrium during the ramp. 3. During application of sufficiently low concentrations of full agonists (carbachol, (ACh) and partial agonists (choline and decamethonium) the I--V 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-fold change in conductance occurring for about 50 mV potential shift. 4. 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 micrometer) the I--V relation became almost straight. 5. 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. 6. 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. 7. I--V relations for full agonists at high concentrations were obtained after alpha-bungarotoxin pre-treatment. During application of carbachol (400--500 micrometer) and ACh (30--40 micrometer; after complete inhibition of acetylcholinesterase activity) the I--V relation of end-plate membrane is much less curved than during application of low concentrations. 8. It is concluded that 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 anaesthetic' action in addition to their agonist activity.