Inotropic effects of the K+ channel blocker TEA on dystrophic (mdx and dy/dy) mouse diaphragm

K+ channels regulate diaphragm resting membrane potential and action potent ial duration, and hence force. Certain blockers of these channels, e.g. tet raethylammonium (TEA), increase twitch force of normal diaphragm. To furthe r 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/d y) was studied in vitro. Diaphragm from both models was significantly weake r than diaphragm from control animals. TEA (10 mM) increased twitch force o f 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 90.2%, P<0 .02). Absolute force increases normalized for cross-sectional area were com parable for healthy and diseased diaphragm, however. These findings indicat e that TEA increases force of both dystrophin-deficient and merosin-deficie nt dystrophic mouse diaphragm muscle. <(c)> 2001 Elsevier Science B.V. All rights reserved.