Mechanisms of Ionophore Toxicoses: Laidlomycin Propionate Toxicosis in the Horse and Monensin, Laidlomycin, and Laidlomycin Propionate in Muscle Cultures
Cellular effects of monensin, laidlomycin, and LP were evaluated after 24-hour exposure in 3-day (myoblasts) and 14-day ($>$90% myotubes) cultures of E-63 rat skeletal muscle cells. Each of these ionophores induced dose-dependent increases in lactate concentrations, decreases in pyruvate concentrations, and decreases in accumulations of NR. Cultures of both myoblasts and myotubes responded similarly, except that myoblasts had greater lactate concentrations than myotubes. Minimum toxic concentrations were 0.1 $\mu$M for each ionophore in both ages of cultures. Concentrations that inhibited NR accumulation by 50% were similar for all three ionophores in both ages of cultures. However, cytotoxic effects of these ionophores were at least partially reversible, as indicated by significant increases in NR accumulation after ionophore removal and incubation for an additional 24 hours. Cytotoxicity of monensin or LP, as indicated by NR accumulation and lactate concentrations, was not affected by decreased media concentrations of potassium, sodium, or calcium. Similarly, cytotoxicity was not influenced by addition of nifedipine, verapamil, or magnesium.
University of Illinois - Urbana-Champaign
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University of Illinois at Urbana-Champaign