The effect of nitrate, iodide and bromide on the duration of the active state in skeletal muscle

Abstract

If a frog’s skeletal muscle is soaked in modified Ringer’s fluid, containing bromide, nitrate or iodide in place of chloride, the tension and duration of a twitch, and its heat production, are largely increased, in the order Br<NO 3 <I. In a tetanic contraction, however, the tension, the heat production and the velocity of shortening under any load are unaffected. The primary effect of these anions, acting on the excitable surface of the muscle fibres, is to increase the duration of the active state after a shock; the increased tension and heat in a twitch result from this. The rate at which the effect comes on after sudden immersion of a muscle in iodide-Ringer depends solely on the rate at which iodide diffuses into the interspaces between the fibres; the rate of penetration of iodide into the fibres is very slow. The effect is not due to any direct action of the anion on the contractile mechanism, for (1) it passes off rapidly, when a muscle after long soaking in iodide-Ringer is transferred to chloride-Ringer, although iodide remains inside for a long time, and (2) the tetanic contraction is unaffected. If the fundamental 'unit’ of contraction were a cycle of events triggered by excitation and then running its own course to completion, the duration of the active state would be an intrinsic property of the contractile mechanism and would not depend on something outside it. But if the active contractile state is set up and maintained in the interior by some influence transmitted from the excitable surface outside, its duration would depend on the time course of the responsible process at the surface. The facts ( a ) that the duration is greatly affected by the presence of, for example, iodide in the interspaces between the fibres, at a time when there is practically none of it inside the fibres, and ( b ) that the effect rapidly passes off as iodide is removed from the interspaces although a large amount of it may still be inside, is decisive evidence for the second view. These abnormal anions somehow affect the time course of the process, started by excitation, in the surface of the fibres from which the active contractile state is transmitted into and maintained in the interior. This exposes a new link in the chain of events connecting excitation with contraction.