Pharmacological studies of excitation-contraction coupling in skeletal muscle.

The use of drugs in the study of excitation-contraction (E-C) coupling in skeletal muscle during the 25-30 years and the role of these studies in the development of the "trigger-calcium" hypothesis was reviewed. In early studies, caffeine was used as a tool to test the function of the intracellular contraction apparatus when the twitch or depolarization contracture was eliminated by a procedure that was thought to block the coupling part of the E-C coupling process. Later it was shown that caffeine produced contractures by releasing Ca2+ ions from intracellular binding sites and then that caffeine produced this effect by sensitizing the sarcoplasmic reticulum to Ca2+-induced Ca2+ release. More recently, organic calcium channel blocking drugs (verapamil, D-600, and nitrendipine) were used to confirm earlier results showing that depolarization contractures but not twitches require the entrance into the cells via the slow Ca2+ channels of extracellular calcium ions for E-C coupling. Most recently, we have investigated the effects of TMB-8 (8-(diethylamino)-octyl-3,4,5-trimethoxybenzoate) on E-C coupling in frog skeletal muscle. This compound was shown by other workers to act in several tissues by stabilizing Ca2+ bound at intracellular sites. It was found that at the appropriate concentration TMB-8 blocked twitches but neither high K+ nor caffeine induced contractures. These results suggest that TMB-8 blocks twitches by preventing the release of Ca2+ ions bound to the intracellular surface of the t-tubular membrane, which is often called the store of "trigger-calcium" ions.(ABSTRACT TRUNCATED AT 250 WORDS)
AuthorsG B Frank
JournalCanadian journal of physiology and pharmacology (Can J Physiol Pharmacol) Vol. 65 Issue 4 Pg. 711-6 (Apr 1987) ISSN: 0008-4212 [Print] CANADA
PMID2440545 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Calcium Channel Blockers
  • Ion Channels
  • Caffeine
  • 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate
  • Gallic Acid
  • Potassium
  • Calcium
  • Animals
  • Caffeine (pharmacology)
  • Calcium (metabolism)
  • Calcium Channel Blockers (pharmacology)
  • Gallic Acid (analogs & derivatives, pharmacology)
  • Ion Channels (physiology)
  • Muscle Contraction (drug effects)
  • Muscles (physiology)
  • Potassium (pharmacology)
  • Rana pipiens

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