TMB-8 can block twitches without blocking high K+ or caffeine induced contractures in frog's skeletal muscle.
TMB-8 [8-(diethylamino)-octyl-3,4,5-trimethoxybenzoate] 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 X 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.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D009132:Muscles / Q000187:drug effects*; D011188:Potassium / Q000494:pharmacology*; D011894:Rana pipiens
D002110:Caffeine; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D011188:Potassium; D002118:Calcium