Positive Inotropic Effects of Low dATP/ATP Ratios on Mechanics and Kinetics of Porcine Cardiac Muscle

AbstractSubstitution of 2′-deoxy ATP (dATP) for ATP as substrate for actomyosin results in significant enhancement of in vitro parameters of cardiac contraction. To determine the minimal ratio of dATP/ATP (constant total NTP) that significantly enhances cardiac contractility and obtain greater understanding of how dATP substitution results in contractile enhancement, we varied dATP/ATP ratio in porcine cardiac muscle preparations. At maximum Ca2+ (pCa 4.5), isometric force increased linearly with dATP/ATP ratio, but at submaximal Ca2+ (pCa 5.5) this relationship was nonlinear, with the nonlinearity evident at 2–20% dATP; force increased significantly with only 10% of substrate as dATP. The rate of tension redevelopment (kTR) increased with dATP at all Ca2+ levels. kTR increased linearly with dATP/ATP ratio at pCa 4.5 and 5.5. Unregulated actin-activated Mg-NTPase rates and actin sliding speed linearly increased with the dATP/ATP ratio (p