Protein kinase A changes calcium sensitivity but not crossbridge kinetics in human cardiac myofibrils

Walker JS, Walker LA, Margulies K, Buttrick P, de Tombe P. Protein kinase A changes calcium sensitivity but not crossbridge kinetics in human cardiac myofibrils. Am J Physiol Heart Circ Physiol 301: H138-H146, 2011. First published April 15, 2011; doi:10.1152/ajpheart.00838.2010.-We investigated the effect of PKA treatment (1 U/ml) on the mechanical properties of isolated human cardiac myofibrils. PKA treatment was associated with significant incorporation of radiolabeled phosphate into several sarcomeric proteins including troponin I and myosin binding protein C and was also associated with a right shift in the tension-pCa relation (Delta pCa50 = 0.2 +/- 0.1). PKA treatment also caused right shifts in the pCa dependence of the rate of tension development, tension redevelopment, and the linear and exponential phases of myofibril relaxation. However, there was no change in the same measures of crossbridge turnover when expressed as a function of tension. We conclude that the changes in crossbridge kinetics as a function of calcium concentration reflect a reduced tension due to a lower calcium sensitivity and that the relationship between crossbridge kinetics and tension was unchanged, indicating no direct effect of PKA treatment on crossbridge cycling.