CAFFEINE EFFECTS ON RADIOCALCIUM MOVEMENT IN NORMAL AND DENERVATED RAT SKELETAL MUSCLE

¹ Division of Physiology, Institute for Muscle Disease, New York

In test of the suggestion (Gutmann and Sandow, Life Sci. 4: 149, 1965) that denervation sensitizes rat extensor digitorum longus (EDL) muscles to produce caffeine (20 mM) contracture by increasing the mobility of the muscle's Ca, we find that caffeine-induced influx and efflux of Ca⁴⁵ are much greater in the 6-day denervated muscle than in the normal one. Denervation alone, like caffeine alone, produces a small increase in flux and no contracture. Experiments with C¹⁴-caffeine show that the normal and the denervated EDL muscles are equally (and highly) permeable to caffeine; and thus the great sensitivity of the denervated muscles to caffeine is not ascribable to a greater permeability to the drug. Tenotomy, like denervation, causes atrophy but produces insignificant flux and contracture changes, and hence the denervation-induced alterations do not result from atrophy as such but from loss of some special neurotrophic influence. Combining the results of other workers with ours, we conclude that the increased fluxes of Ca⁴⁵ induced especially by caffeine in our experiments indicate increases in Ca2⁺-release from the sarcoplasmic reticulum (SR) and corresponding enhancement of free, sarcoplasmic Ca²⁺. And we thus infer that normal rat EDL muscles fail to produce caffeine contracture because their SR is relatively resistant to Ca release by caffeine and that denervation increases susceptibility to caffeine contracture by sensitizing the SR to the Ca-releasing action of caffeine.