Published online before print November 15, 2001, doi: 10.1161/hh2401.101908
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Submitted on June 26, 2001
Revised on November 2, 2001
Accepted on November 2, 2001
Power Output Is Increased After Phosphorylation of Myofibrillar Proteins in Rat Skinned Cardiac Myocytes
From the Department of Physiology, University of Missouri School of Medicine, Columbia, Mo.
* To whom correspondence should be addressed. E-mail: mcdonaldks{at}health.missouri.edu.
ß-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 Ca2+ sensitivity of force. PKA also significantly increased both maximal force (25.4±8.3 versus 31.6±11.3 µN [P<0.001, n=12]) and peak absolute power output (2.48±1.33 versus 3.38±1.52 µW/mg [P<0.05, n=5]) during maximal Ca2+ 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 
20% during maximal Ca2+ activations (n=5) and 33% during half-maximal Ca2+ 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 ß-adrenergic stimulation.
Key words: cardiac myocytes • ß-adrenergic stimulation • cardiac contractility • sarcomere proteins • protein kinase A
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