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Journal Article

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


Sakmann,  Bert
Department of Cell Physiology, Max Planck Institute for Medical Research, Max Planck Society;

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Adams, P. R., & Sakmann, B. (1978). A comparison of current‐voltage relations for full and partial agonists. Journal of Physiology, 283(1), 621-644. doi:10.1113/jphysiol.1978.sp012523.

Cite as: http://hdl.handle.net/21.11116/0000-0001-26C1-A
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.