IN-VITRO TOXICITY SCREENING USING CULTURED RAT SKELETAL-MUSCLE CELLS .2. AGENTS AFFECTING EXCITABLE-MEMBRANES

The screening of chemicals for their potential to interfere with excit able cell membranes should be an important element of in vitro testing for acute toxicity. The suitability for this purpose of a test system using primary cultured rat skeletal muscle cells was evaluated. The t est protocol involved the determination of the concentration-dependent effects on three endpoints: (1) spontaneous contractility, (2) membra ne integrity and (3) energy metabolism. The chemicals investigated wer e: NaCl, KCI and CaCl2; cardiac glycosides (ouabain, digoxin); sodium channel toxins (tetrodotoxin, saxitoxin, veratridine, Anemonia sulcata toxin II, Bolocera tuediae toxin II); an acetylcholine agonist (carba chol); a calcium antagonist (D600) and three membrane-directed insecti cides (deltamethrin, DDT, lindane). The response pattern of most of th ese substances-alteration of contractility at concentrations that neit her affected the energy metabolism nor were cytolethal-characterized t hem as acting either on the excitable membrane or on the excitation-co ntraction coupling and the contractile apparatus. The results indicate that the test system is suited to assess chemical effects resulting i n: (i) changes of resting membrane and threshold potentials, (ii) alte red sodium channel function, (iii) opening of endplate channels, (iv) blockade of calcium channels, and (v) inhibition of Na+/K+-ATPase.