Modulation of the rate of cardiac muscle contraction by troponin C constructs with various calcium binding affinities.
We investigated whether changing thin filament Ca(2+) sensitivity alters the rate of contraction, either during normal cross-bridge cycling or when cross-bridge cycling is increased by inorganic phosphate (P(i)). We increased or decreased Ca(2+) sensitivity of force production by incorporating into rat skinned cardiac trabeculae the troponin C (TnC) mutants V44QTnC(F27W) and F20QTnC(F27W). The rate of isometric contraction was assessed as the rate of force redevelopment (k(tr)) after a rapid release and restretch to the original length of the muscle. Both in the absence of added P(i) and in the presence of 2.5 mM added P(i) 1) Ca(2+) sensitivity of k(tr) was increased by V44QTnC(F27W) and decreased by F20QTnC(F27W) compared with control TnC(F27W); 2) k(tr) at submaximal Ca(2+) activation was significantly faster for V44QTnC(F27W) and slower for F20QTnC(F27W) compared with control TnC(F27W); 3) at maximum Ca(2+) activation, k(tr) values were similar for control TnC(F27W), V44QTnC(F27W), and F20QTnC(F27W); and 4) k(tr) exhibited a linear dependence on force that was indistinguishable for all TnCs. In the presence of 2.5 mM P(i), k(tr) was faster at all pCa values compared with the values for no added P(i) for TnC(F27W), V44QTnC(F27W), and F20QTnC(F27W). This study suggests that TnC Ca(2+) binding properties modulate the rate of cardiac muscle contraction at submaximal levels of Ca(2+) activation. This result has physiological relevance considering that, on a beat-to-beat basis, the heart contracts at submaximal Ca(2+) activation.
Norman
Catalina
C
Department of Physiology and Cell Biology, Ohio State University, Columbus, Ohio 43210, USA.
Rall
Jack A
JA
Tikunova
Svetlana B
SB
Davis
Jonathan P
JP
D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D066298:In Vitro Techniques; D007537:Isometric Contraction; D007700:Kinetics; D008297:Male; D008955:Models, Cardiovascular; D053580:Muscle Strength; D009154:Mutation; D009200:Myocardial Contraction; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D019209:Troponin C / Q000235:genetics / Q000378:metabolism*; D019210:Troponin I / Q000378:metabolism
D010710:Phosphates; D019209:Troponin C; D019210:Troponin I; D002118:Calcium