Action of caffeine in excitation‐contraction coupling of frog skeletal muscle fibres.

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Abstract
Frog sartorius muscle bathed in 1 mM caffeine generated brief asynchronous contraction of individual sarcomeres, sarcomeric oscillations, and propagated contractile waves. Analysis of cinematographic records showed that during sarcomeric oscillations the sarcomere length decreased and the distribution of sarcomere lengths was wider than in controls. Caffeine produced sarcomeric oscillations in K-depolarized muscle fibers and, to a limited extent, in glycerol-treated muscle fibers. Treatment of muscle with dantrolene sodium blocked production of sarcomeric oscillations by caffeine. In caffeine-treated muscle fibers, electrically produced depolarization initiated or increased the frequency of sarcomeric oscillations and electrical hyperpolarization diminished the frequency or stopped sarcomeric oscillations. Caffeine solution bathing a muscle undergoing sarcomeric oscillations (the perfusate), when applied to a fresh muscle, initiated sarcomeric oscillations with a relatively short latency. An UV-absorbance peak at 245 nm developed in the caffeine solution bathing a muscle undergoing sarcomeric oscillations. A contraction-regulating substance (oscillogen) was released from a muscle undergoing sarcomeric oscillations. From results of selective dialysis and gel permeation chromatography, the MW of the oscillogen was estimated to be 700-1000 daltons. The oscillogen is an apparently normally occurring substance which functions in excitation-contraction coupling at the T-tubule terminal cistern junction in skeletal muscle.