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          Institute: MPI für medizinische Forschung     Collection: Abteilung Zellphysiologie     Display Documents

ID: 22029.0, MPI für medizinische Forschung / Abteilung Zellphysiologie
A comparison of current voltage relations of full and partial agonists
Translation of Title:A comparison of current voltage relations of full and partial agonists
Authors:Adams, P. R.; Sakmann, Bert
Date of Publication (YYYY-MM-DD):1978
Title of Journal:Journal of Physiology
Journal Abbrev.:J. Physiol.
Start Page:621
End Page:644
Review Status:Peer-review
Audience:Experts Only
Intended Educational Use:No
Abstract / Description: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.
External Publication Status:published
Document Type:Article
Communicated by:Wulf Kaiser
Affiliations:MPI für medizinische Forschung/Abteilung Zellphysiologie/
Identifiers:URI:http://www.jphysiol.org/cgi/content/abstract/283/1... [Abstract]
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