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Abstract

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