Inotrophic effects of the K(+) channel blocker TEA on dystrophic (mdx and dy/dy) mouse diaphragm.
K(+) channels regulate diaphragm resting membrane potential and action potential duration, and hence force. Certain blockers of these channels, e.g. tetraethylammonium (TEA), increase twitch force of normal diaphragm. To further address whether these agents may be useful in the treatment of diaphragm weakness, studies examined the effects of TEA on force of overtly diseased muscle. Diaphragm from two mouse models of muscular dystrophy (mdx and dy/dy) was studied in vitro. Diaphragm from both models was significantly weaker than diaphragm from control animals. TEA (10 mM) increased twitch force of both mdx diaphragm (P<0.005) and dy/dy diaphragm (P<0.0005), as well as force of diaphragm from non-diseased animals. The percent force increase of mdx diaphragm was at least as great as that of non-diseased muscle (15.3 vs 9.2%, P=0.14), and the percent force increase of dy/dy diaphragm was significantly greater than that of non-diseased muscle (22.7 vs 10.2%, P<0.02). Absolute force increases normalized for cross-sectional area were comparable for healthy and diseased diaphragm, however. These findings indicate that TEA increases force of both dystrophin-deficient and merosin-deficient dystrophic mouse diaphragm muscle.
van Lunteren
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Department of Medicine (Pulmonary), Case Western Reserve University and Cleveland VA Medical Center, 10701 East Boulevard, Cleveland, OH 44106, USA. exv4@po.cwru.edu
Manubay
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D000818:Animals; D003964:Diaphragm / Q000187:drug effects* / Q000503:physiopathology*; D016189:Dystrophin / Q000172:deficiency / Q000502:physiology; D066298:In Vitro Techniques; D007797:Laminin / Q000172:deficiency / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D008817:Mice, Mutant Strains; D009119:Muscle Contraction / Q000187:drug effects*; D009137:Muscular Dystrophy, Animal / Q000188:drug therapy* / Q000503:physiopathology*; D026902:Potassium Channel Blockers; D019789:Tetraethylammonium / Q000494:pharmacology*
D016189:Dystrophin; D007797:Laminin; D026902:Potassium Channel Blockers; D019789:Tetraethylammonium