EFFECT OF IONOPHORE X‐537A ON DESENSITIZATION RATE AND TENSION DEVELOPMENT IN POTASSIUM‐DEPOLARIZED MUSCLE FIBRES

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Abstract
1 The effects of the ionophore X-537A were studied on carbamylcholine (carbachol)-induced desensitization and on tension development in relaxed potassium-depolarized frog sartorius muscles. 2 X-537A accelerated carbachol-induced desensitization in Ca2+-deficient solutions without having any effect on the conductance of the membrane in the absence of carbachol or on the extent of the carbachol-induced increase in conductance. 3 In Ca2+-deficient solution, the acceleration of desensitization by the ionophore was concentration-dependent. No effect was observed with concentrations less than 5 μm and maximal acceleration was evident with 10 μm. 4 The influence of X-537A on desensitization was time-dependent. At 20 μm X-537A, there was a marked acceleration of desensitization by the end of 5 min exposure. An additional gradual acceleration occurred during a 5 to 30 min treatment. No acceleration of desensitization was evident when X-537A was simultaneously applied with carbachol to the end-plate region without prior exposure to the ionophore. 5 Desensitization also was accelerated by 30 min exposure to 20 μm X-537A in solutions containing Ca2+ or deficient in both Mg2+ and Ca2+; the rate being increased 2.8-fold in Ca2+-containing solutions, 2.9-fold in Ca2+-deficient solutions containing Mg2+, and 2.5-fold in divalent cation-deficient solutions. 6 Tension development gradually occurred in relaxed potassium-depolarized muscle preparations exposed to 20 μm X-537A. The onset of tension development occurred only after approximately 25 min of exposure both in preparations kept in Ca2+-deficient or Ca2+-containing solutions. By the end of 90 min in the ionophore, the tension developed was approximately 12% and 23% of the initial potassium contracture in those preparations maintained in the Ca2+-deficient or Ca2+-containing solutions, respectively. 7 We assume that the increase in desensitization rate following exposure to X-537A results from an elevation of the intracellular Ca2+ concentration. That muscle tension gradually increased during exposure to the ionophore supports this conclusion. The acceleration of desensitization by X-537A in the absence of external Ca2+ supports the view that the site of calcium acceleration is not on the external surface of the end-plate membrane either at or near the agonist-recognition site but rather on the inner surface.