Protein kinase A increases the tension cost and unloaded shortening velocity in skinned rat cardiac muscle.
To address controversies concerning the effect of beta-adrenergic stimulation on the rate of cross-bridge cycling in cardiac muscle, we measured ca(2+)-induced isometric tension development, unloaded shortening velocity (Vmax) and ATPase activity of demembranated (Triton X-100 skinned) rat right ventricular trabeculae before and after treatment with the catalytic subunit of protein kinase A (PKA), which is known to mimic the action of beta-adrenergic agonists in demembranated preparations. PKA treatment (1 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 state tension) without changing the steepness of the pCa-tension relation and the maximum Ca(2+)-activated tension; Vmax, as determined by the slack test, was increased for a given pCa value, despite the reduced level of isometric tension. PKA treatment also shifted the pCa-ATPase activity to the right slightly from 5.47 to 5.40 at pCa50 (the [Ca2+] required for half maximal ATPase activity), but increased the ATPase activity during a given level of steady isometric tension generation, resulting in a 33% increase of the tension cost (ATPase activity/tension). All the results obtained strongly suggest that, in rat right ventricular trabeculae, beta-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 Ca(2+)-sensitivity of the contractile system.
Saeki
Y
Y
Department of Physiology, Tsurumi University School of Dental Medicine, Yokohama, Japan.
Kobayashi
T
T
Minamisawa
S
S
Sugi
H
H
D000251:Adenosine Triphosphatases / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism / Q000494:pharmacology*; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology*; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D012212:Rheology; D016276:Ventricular Function
D011943:Receptors, Adrenergic, beta; D017868:Cyclic AMP-Dependent Protein Kinases; D000251:Adenosine Triphosphatases; D002118:Calcium