CAFFEINE EFFECTS ON RADIOCALCIIJM MOVEMENT IN NORMAL AND DENERVATED RAT SKELETAL MUSCLE’

ISAACSON, ALLEN AND ALEXANDER SANDOW: Caffeine effects on radiocalcium movement in normal and denervated rat skeletal muscle. J. Pharmac. exp. Ther. 155: 376-388, 1967. In test of the suggestion (Gutmann and Sandow, Life Sci. 4: 149, 1965) that de-nervation 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 Ca’ 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 sensi-tivity 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 re-suits of other workers with ours, we conclude that the increased fluxes of Ca’ induce