PKA-induced phosphorylation of myofibrillar proteins directly increases the power output-generating capacity of skinned cardiac myocytes, contributing to greater contractility after beta-adrenergic stimulation.
beta-Adrenergic stimulation increases stroke volume in mammalian hearts as a result of protein kinase A (PKA)-induced phosphorylation of several myocyte proteins. This study investigated whether PKA-induced phosphorylation of myofibrillar proteins directly affects myocyte contractility. To test this possibility, we compared isometric force, loaded shortening velocity, and power output in skinned rat cardiac myocytes before and after treatment with the catalytic subunit of PKA. Consistent with previous studies, PKA increased phosphorylation levels of myosin binding protein C and troponin I, and reduced Ca(2+) sensitivity of force. PKA also significantly increased both maximal force (25.4+/-8.3 versus 31.6+/-11.3 microN P<0.001, n=12) and peak absolute power output (2.48+/-1.33 versus 3.38+/-1.52 microW/mg P<0.05, n=5) during maximal Ca(2+) activations. Furthermore, PKA elevated power output at nearly all loads even after normalizing for the increase in force. After PKA treatment, peak normalized power output increased approximately 20% during maximal Ca(2+) activations (n=5) and approximately 33% during half-maximal Ca(2+) activations (n=9). These results indicate that PKA-induced phosphorylation of myofibrillar proteins increases the power output-generating capacity of skinned cardiac myocytes, in part, by speeding the step(s) in the crossbridge cycle that limit loaded shortening rates, and these changes likely contribute to greater contractility in hearts after beta-adrenergic stimulation.
Herron et al. (Fri,) studied this question.