Characterization of secophalloidin-induced force loss in cardiac myofibrils

Secophalloidin (SPH) is known to cause in cardiac myofibrils force without Ca²⁺ (half-maximal effect ∼2 mM) followed by irreversible loss of Ca²⁺-activated force. At maximal Ca²⁺ activation, SPH increases force (half-maximal effect < 0.1 mM). We found that SPH at low concentration (0.5 mM) did not cause either force activation or force loss at pCa 8.7, but both of these effects did occur when force was activated by Ca²⁺. The force loss was prevented when SPH was applied during rigor or in the presence of 2, 3-butanedione monoxime (85 mM). Furthermore, studying muscle in which the force was previously reduced by SPH (up to 50%) did not reveal significant changes in Ca²⁺ sensitivity and cooperativity of Ca²⁺-activation or qualitative alterations in SPH-induced changes in Ca²⁺-activated contraction. Data suggest that the force loss is mediated by cycling cross-bridges, and might reflect a reduction in force generated by individual cross-bridges.