PT - JOURNAL ARTICLE AU - Allen Isaacson AU - Alexander Sandow TI - CAFFEINE EFFECTS ON RADIOCALCIUM MOVEMENT IN NORMAL AND DENERVATED RAT SKELETAL MUSCLE DP - 1967 Feb 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 376--388 VI - 155 IP - 2 4099 - http://jpet.aspetjournals.org/content/155/2/376.short 4100 - http://jpet.aspetjournals.org/content/155/2/376.full SO - J Pharmacol Exp Ther1967 Feb 01; 155 AB - 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. © 1967 by The Williams & Wilkins Company