Modulation of the rate of cardiac muscle contraction by troponin C constructs with various calcium binding affinities

Abstract

We investigated whether changing thin filament Ca2+sensitivity alters the rate of contraction, either during normal cross-bridge cycling or when cross-bridge cycling is increased by inorganic phosphate (Pi). We increased or decreased Ca2+sensitivity of force production by incorporating into rat skinned cardiac trabeculae the troponin C (TnC) mutants V44QTnCF27Wand F20QTnCF27W. The rate of isometric contraction was assessed as the rate of force redevelopment ( ktr) after a rapid release and restretch to the original length of the muscle. Both in the absence of added Piand in the presence of 2.5 mM added Pi1) Ca2+sensitivity of ktrwas increased by V44QTnCF27Wand decreased by F20QTnCF27Wcompared with control TnCF27W; 2) ktrat submaximal Ca2+activation was significantly faster for V44QTnCF27Wand slower for F20QTnCF27Wcompared with control TnCF27W; 3) at maximum Ca2+activation, ktrvalues were similar for control TnCF27W, V44QTnCF27W, and F20QTnCF27W; and 4) ktrexhibited a linear dependence on force that was indistinguishable for all TnCs. In the presence of 2.5 mM Pi, ktrwas faster at all pCa values compared with the values for no added Pifor TnCF27W, V44QTnCF27W, and F20QTnCF27W. This study suggests that TnC Ca2+binding properties modulate the rate of cardiac muscle contraction at submaximal levels of Ca2+activation. This result has physiological relevance considering that, on a beat-to-beat basis, the heart contracts at submaximal Ca2+activation.