PROTEIN-KINASE A DOES NOT ALTER ECONOMY OF FORCE MAINTENANCE IN SKINNED RAT CARDIAC TRABECULAE

Recent mechanical, biochemical, and energetic experiments have suggest ed 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 for ce maintenance. The present study tested this hypothesis directly by m easuring 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 diff raction, and ATP consumption was assessed by an enzyme-coupled optical technique. Force-[Ca2+] relations were fit to a modified Hill equatio n. Force dependency of the rate of ATP consumption was analyzed by mul tiple linear regression analysis. beta-Adrenergic stimulation was mimi cked by incubation of the skinned muscle preparation with the catalyti c subunit of protein kinase A (PKA). Treatment with PKA (3 mu g/mL, 40 minutes) induced a significant (65+/-23%, P=.01) increase in [Ca2+] r equired for half-maximal steady state force, whereas the steepness of the force-[Ca2+] relation was not affected. The rate of ATP consumptio n was linearly correlated with steady state force, regardless of PKA t reatment status (P<.001). However, neither the slope nor the intercept was affected by PKA treatment. Hence, PKA treatment did not affect ei ther the maximum rate of ATP consumption or the economy of force maint enance. These results suggest that beta-adrenergic stimulation does no t alter the rate-limiting step of cross-bridge cycling during isometri c contraction in myocardium.