PKA accelerates rate of force development in murine skinned myocardium expressing alpha- or beta-tropomyosin

In myocardium, protein kinase A (PKA) is known to phosphorylate troponin I (TnI) and myosin-binding protein-C (MyBP-C). Here, we used skinned myocardi al preparations from nontransgenic (NTG) mouse hearts expressing 100% alpha -tropomyosin (alpha -Tm) to examine the effects of phosphorylated TnI and MyBP-C on Ca2+ sensitivity of force and the rate constant of force redevelo pment (k(tr)). Experiments were also done using transgenic (TG) myocardium expressing similar to 60% beta -Tm to test the idea that the alpha -Tm isof orm is required to observe the mechanical effects of PKA phosphorylation. C ompared with NTG myocardium, TG myocardium exhibited greater Ca2+ sensitivi ty of force and developed submaximal forces at faster rates. Treatment with PKA reduced Ca2+ sensitivity of force in NTG and TG myocardium, had no eff ect on maximum k(tr) in either NTG or TG myocardium, and increased the rate s of submaximal force development in both kinds of myocardium. These result s show that PKA-mediated phosphorylation of myofibrillar proteins significa ntly alters the static and dynamic mechanical properties of myocardium, and these effects occur regardless of the type of Tm expressed.