The motor endplate of frog sartorius muscle was voltage clamped and the peak current to different concentrations of acetylcholine and carbachol applied in the perfusing fluid was measured. Perfusing fluid was hypertonic in order to suppress contractions. Current responses were smooth and reached a peak value within 2–5 s. The dose-response curve was usually linear even with concentrations of 10-2 M acetylcholine, indicating that the conductance change was probably proportional to the concentration of acetylcholine or carbachol. With high concentrations nonlinearity sometimes appeared but in these cases the fast onset of desensitization appeared to be preventing the current response from reaching its expected peak amplitude. When the depolarization produced by acetylcholine in a non-voltage-clamped endplate was measured the dose-response curve was hyperbolic. This relationship was imposed by the electrical properties of the endplate membrane and its surrounding sarcolemma, and could be predicted if the input resistance of the fiber was known. Experiments were also done on slow muscle fibers. Depolarizing analogues of acetylcholine had similar effects to acetylcholine. d-Tubocurarine reduced the proportionality constant between concentration of acetylcholine and conductance change, and this resulted in a parallel shift of the log-concentration depolarization curve. A linear dose-response curve was unexpected within the context of current theories of drug action.
Article| July 01 1973
A Linear Dose-Response Curve at the Motor Endplate
From the Department of Pharmacology, Cambridge University, Cambridge, England.
Dr. Harrington's present address is c/o Dr. J. Harrington, The Rockefeller University, New York 10021.
Received: September 20 1971
Online Issn: 1540-7748
Print Issn: 0022-1295
Copyright © 1973 by The Rockefeller University Press
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Lesley Harrington; A Linear Dose-Response Curve at the Motor Endplate . J Gen Physiol 1 July 1973; 62 (1): 58–76. doi: https://doi.org/10.1085/jgp.62.1.58
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