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

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.