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

1. Frog sartorius muscle bathed in 1 mM-caffeine generates brief asynchronous contraction of individual sarcomeres, 'sarcomeric oscillations', and propagated contractile waves. 2. Analysis of cinematographic records shows that during sarcomeric oscillations the sarcomere length decreases and the distribution of sarcomere lengths is wider than in controls. 3. Caffeine can produce sarcomeric oscillations in K depolarized muscle fibres and, to a limited extent, in glycerol-treated muscle fibres. 4. Treatment of muscle with dantrolene sodium blocks production of sarcomeric oscillations by caffeine. 5. In caffeine-treated muscle fibres, electrically produced depolarization could initiate or increase the frequency of sarcomeric oscillations, and electrical hyperpolarization diminishes the frequency or stops sarcomeric oscillations. 6. Caffeine solution bathing a muscle undergoing sarcomeric oscillations (the perfusate), when applied to a fresh muscle, initiates sarcomeric oscillations with a relatively short latency. 7. An U.V.-absorbance peak at 245 nm develops in the caffeine solution bathing a muscle undergoing sarcomeric oscillations. 8. It was found that a contraction-regulating substance (oscillogen) is released from a muscle undergoing sarcomeric oscillations. From results of selective dialysis and gel permeation chromatography, the molecular weight of the oscillogen is estimated to be between 700-1000 daltons. 9. It is proposed that the oscillogen is a normally occurring substance which functions in excitation-contraction coupling at the T-tubule terminal cistern junction in skeletal muscle.