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Thin filament regulation of muscle contraction is believed to be mediated by both Ca 2+ and strongly bound myosin cross-bridges. We found that secophalloidin (SPH, 5-8 mM) activates cross-bridge cycling without Ca 2+ causing isometric force comparable to that induced by Ca 2+ . At saturated [SPH], Ca 2+ further increased force by 20%. SPH-induced...