TMB-8 can block twitches without blocking high K + or caffeine induced contractures in frog's skeletal muscle

Abstract

TMB-8 [8-(diethylamino)-octyl-3,4, 5trimethoxybenzoate] is known to inhibit calcium ion dependent processes in several tissues by stabilizing some intracellular stores of membrane-bound calcium. TMB-8 was used to study the excitation-contraction (E-C) coupling process in frog's skeletal muscle. TMB-8 (5 × 10 −5 − 10 −4 M) blocked electrically evoked twitches but not high K + (123 mM)- or caffeine (2.36 mM)-induced contractures in isolated, curarized toe muscles. TMB-8 (10 −4 M) produced a small decrease (16%) in the action potential of frog's sartorius muscle fibres. However, reducing extracellular Na + to 44.7 mM produced a similar reduction (17%) in action potential amplitude but did not suppress the twitch; i.e. it produced only a small increase (about 10%) in twitch amplitude. It is known that potassium contractures are produced by extracellular Ca ++ ions which enter through calcium channels in the t-tubules and that caffeine produces contractures by sensitizing the sarcoplasmic reticulum to Ca ++-induced Ca ++ release. The present results suggest that TMB-8 blocks twitches by preventing the release of Ca ++ ions bound to the intracellular surface of the t-tubular membrane which is often called the store of ‘trigger-calcium’ ions.