Influences of protein kinase A and D-cAMP on actin-myosin interaction and energy consumption of cardiac muscles.
To address controversies concerning the effects of beta-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 demembranated 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 (I U/microliter, 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, beta-adrenergic stimulation may increase the rate of cross-bridge cycling by increasing the rate of crossbridge detachment from actin through a PKA-mediated mechanism, although PKA reduces the Ca(2+)-sensitivity of the contractile system.
Saeki
Y
Y
Department of Physiology, School of Dental Medicine, Tsurumi University, Yokohama, Japan.
Kobayashi
T
T
Takigiku
K
K
Sugi
H
H
D000249:Adenosine Monophosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000494:pharmacology*; D004734:Energy Metabolism; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D016276:Ventricular Function
D000249:Adenosine Monophosphate; D017868:Cyclic AMP-Dependent Protein Kinases