Influences of Protein Kinase A and D-Camp on Actin-Myosin Interaction and Energy Consumption of Cardiac Muscles

Abstract

To address controversies concerning the effects of β;-adrenergic stimulation on the rate of myocardial cross-bridge cycling, we measured three mechanical variables, isometric tension development, transient tension response to a step stretch in length (<1% of muscle length), maximum velocity of shortening, and a chemical variable, ATPase activity before and after treatment with the catalytic subunit of protein kinase A (PKA) in demem-branated rat right ventricular trabeculae, and also measured three mechanical variables before and after treatment with D-cAMP in intact ryanodine-induced tetanized preparations. PKA treatment (1 U/μl, 40 min) shifted the pCa-tension relation to the right from 5.41 to 5.26 at pCa₅₀ (the [Ca²⁺] required for half maximal steady tension) without changing the steepness of the pCa-tension relation and the maximum tension. The rate of the transient tension changes was significantly increased after either PKA or D-cAMP treatment (5 mM, 15 min), regardless of the level of isometric tension. Vmax was increased for a given Ca²⁺ concentration after either the PKA or D-cAMP treatment, despite the reduced level of isometric tension. The PKA treatment also shifted the pCa-ATPase activity to the right slightly from 5.47 to 5.40 at pCa₅₀, but increased the ATPase activity during a given level of steady isometric tension generation, resulting in an increased tension cost (ATPase activity/tension). These results suggest that, in rat right ventricular trabeculae, β-adrenergic stimulation may increase the rate of cross-bridge cycling by increasing the rate of cross-bridge detachment from actin through a PKA-mediated mechanism, although PKA reduces the Ca²⁺-sensitivity of the contractile system.