The pathophysiology of myotonia produced by aromatic carboxylic acids
- 7 October 1978
- journal article
- research article
- Published by Wiley in Annals of Neurology
- Vol. 4 (4), 357-365
- https://doi.org/10.1002/ana.410040411
Abstract
A series of nine related aromatic monocarboxylic acids (ACAs) previously shown to inhibit muscle membrane chloride conductance (GCl) selectively in the rat were studied for their ability to produce myotonia. All nine induced characteristic repetitive electrical activity and delayed relaxation in isolated muscle, although the concentrations required for this action varied widely. In each case, myotonia was observed at concentrations that correlated closely with previously determined half‐maximal concentrations for inhibition of GCl. Intracellular recordings from muscle made myotonic with ACA revealed prolonged latencies at rheobase, multiple driven spikes, and self‐sustaining repetitive activity similar to that previously reported in hereditary goat myotonia. Phase‐plane diagrams of membrane action potentials recorded after exposure to the most effective of these compounds suggested little effect on the voltage‐dependent sodium system. The changes seen could be duplicated by simple removal of chloride ion. The expression of repetitive electrical activity in the presence of low membrane GCl depends on ambient temperature and on the concentration of calcium ion. Increasing temperature and decreasing Ca++ predispose toward myotonic activity; converse conditions inhibit myotonia. Myotonia induced by ACA is inhibited by concentrations of diphenylhydantoin that are clinically effective in controlling hereditary myotonia in humans.Keywords
This publication has 27 references indexed in Scilit:
- On the inhibition of muscle membrane chloride conductance by aromatic carboxylic acids.The Journal of general physiology, 1977
- Characteristics of the chloride conductance in muscle fibers of the rat diaphragm.The Journal of general physiology, 1977
- Kinetic and pharmacological properties of the sodium channel of frog skeletal muscle.The Journal of general physiology, 1976
- Negative surface charge near sodium channels of nerve: divalent ions, monovalent ions, and pHPhilosophical Transactions of the Royal Society of London. B, Biological Sciences, 1975
- The Temperature Dependence of Action Potentials in Rat Skeletal Muscle FibresActa Physiologica Scandinavica, 1974
- Diphenylhydantoin and Ion Flux in Lobster NerveArchives of Neurology, 1972
- Divalent Ions and the Surface Potential of Charged Phospholipid MembranesThe Journal of general physiology, 1971
- Cable parameters, sodium, potassium, chloride, and water content, and potassium efflux in isolated external intercostal muscle of normal volunteers and patients with myotonia congenitaJCI Insight, 1971
- Charges and Potentials at the Nerve SurfaceThe Journal of general physiology, 1968
- The After-Potential that Follows Trains of Impulses in Frog Muscle FibersThe Journal of general physiology, 1964