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Use of ion channel blockers in studying the regulation of skeletal muscle contractions

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Summary

Effects of K+- and Cl−-channel blockers on the muscle contraction of mouse diaphragm in response to direct electrical muscle stimulation were studied. K+-channel blockers (0.1–1 mmol/1 4-aminopyridine, 0.4–1.2 mmol/l uranyl nitrate and 2-30 mmol/l tetraethylammonium chloride) and a Cl−-channel blocker (0.01–0.03 mmol/1 9-anthracene carboxylic acid) increased the contractile amplitudes in a limited extent not to exceed over 50% of control. However, the sequential applications of two different channel blockers at a rather low concentration markedly increased the contractile responses mostly over 300% of control except the combination of 4-aminopyridine and uranyl nitrate. It appears that two K+-channel blockers synergistically exerted their effects rather than additionally in the regulation of muscle contractions. Investigation on the possible mechanism of the synergistic action of K+-channel blockers suggested that prolongation of action potential durations was in a linear correlation with the increased contractions. On the other hand, the contractile potentiation induced by combination of K+- and Cl−-channel blockers was attributed to the production of repetitive action potential firings (150±12 Hz) upon a single electrical stimulation. Similar to Cl−-channel blocker, low Cl− as well as low Ca2+ enchanced K+-channel blockers in producing contractile potentiation accompanied with stimulus-bound repetitive discharges. Tetrodotoxin at a concentration of 0.03 μmol/l which did not affect the twitches evoked by electrical stimulations completely inhibited the contractile potentiation induced by the combined application of K+- and Cl−-channel blockers. It was believed that these studies on the contractions of mouse diaphragm carried out in the physiological salt solution provided a better approach in exploring the possible functions of K+- and Cl−-channels in the regulation of skeletal muscle contractions. Moreover, because of the different K+-channels inhibited by these blockers (4-aminopyridine and uranyl nitrate majorly on delayed rectifier K+-channel and tetraethylammonium ion on Ca2+-activated and ATP-sensitive K+-channel), it was concluded that the different types of K+-channels as well as Cl−-channels exert their effects in a synergistic manner on the regulation of the skeletal muscle contractions.

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Authors and Affiliations

  1. Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China

    S. Y. Lin-Skiau, S. Y. Day & W. M. Fu

  2. Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China

    S. Y. Lin-Skiau

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  1. S. Y. Lin-Skiau
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  2. S. Y. Day
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  3. W. M. Fu
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Lin-Skiau, S.Y., Day, S.Y. & Fu, W.M. Use of ion channel blockers in studying the regulation of skeletal muscle contractions. Naunyn-Schmiedeberg's Arch Pharmacol 344, 691–697 (1991). https://doi.org/10.1007/BF00174753

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