Differential effects of bepridil on functional properties of troponin C inslow and fast skeletal muscles

1 Bepridil (BPD) is a pharmacological compound able to bind to the Ca2+ sen sor protein troponin C (TnC), which triggers skeletal muscle contraction up on Ca2+-binding. BPD can thereby modulate the Ca2+-affinity of this protein . 2 The Ca2+-sensitizing action of bepridil was investigated on slow and fast isoforms of TnC from skinned slow and fast skeletal muscle fibres, activat ed by either Ca2+ or Sr2+ ions. 3 Bepridil did not modify the Ca2+ maximal tension of slow and fast fibres, suggesting that binding of the drug to TnC did not induce a change in the number of cross-bridges involved in maximal tension. 4 Sr2+ ions induced lower maximal tension than Ca2+ ions. However, in fast fibres, these lower Sr2+ maximal tensions could be reinforced by bepridil, suggesting an effect of bepridil on the function of site I of fast TnC. 5 Under submaximal tension, bepridil induced an increase in Ca2+ affinity o f TnC in both slow and fast fibres. However, slow fibres were more drug rea ctive than fast fibres, and the increase in tension appeared to be modulate d by the Ca2+ concentration. 6 Thus, bepridil exerted a differential effect on slow and fast fibres. Mor eover, the results suggest that bepridil was more effective when activation conditions were unfavourable.