Protein Kinase A Does Not Alter Economy of Force Maintenance in Skinned Rat Cardiac Trabeculae

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Abstract
Recent mechanical, biochemical, and energetic experiments have suggested that catecholamines may increase the cycling rate of cross-bridges independent of changes in intracellular calcium. An increased rate of cross-bridge cycling is expected to result in decreased economy of force maintenance. The present study tested this hypothesis directly by measuring the rate of ATP consumption in skinned cardiac trabeculae as a function of steady state force. Rat cardiac trabeculae were skinned with Triton X-100. Resting sarcomere length was measured by laser diffraction, and ATP consumption was assessed by an enzyme-coupled optical technique. Force-[Ca2+] relations were fit to a modified Hill equation. Force dependency of the rate of ATP consumption was analyzed by multiple linear regression analysis. β-Adrenergic stimulation was mimicked by incubation of the skinned muscle preparation with the catalytic subunit of protein kinase A (PKA). Treatment with PKA (3 μg/mL, 40 minutes) induced a significant (65±23%, P=.01) increase in [Ca2+] required for half-maximal steady state force, whereas the steepness of the force-[Ca2+] relation was not affected. The rate of ATP consumption was linearly correlated with steady state force, regardless of PKA treatment status (P<.001). However, neither the slope nor the intercept was affected by PKA treatment. Hence, PKA treatment did not affect either the maximum rate of ATP consumption or the economy of force maintenance. These results suggest that β-adrenergic stimulation does not alter the rate-limiting step of cross-bridge cycling during isometric contraction in myocardium.