Effect of troponin I phosphorylation by protein kinase A on length-dependence of tension activation in skinned cardiac muscle fibers.
We examined the effect of troponin I (TnI) phosphorylation by cAMP-dependent protein kinase (PKA) on the length-dependent tension activation in skinned rat cardiac trabeculae. Increasing sarcomere length shifted the pCa (-log[Ca2+])-tension relation to the left. Treatment with PKA decreased the Ca2+ sensitivity of the myofilament and also decreased the length-dependent shift of the pCa-tension relation. Replacement of endogenous TnI with phosphorylated TnI directly demonstrated that TnI phosphorylation is responsible for the decreased length-dependence. When MgATP concentration was lowered in the absence of Ca2+, tension was elicited through rigorous cross-bridge-induced thin filament activation. Increasing sarcomere length shifted the pMgATP (-log[MgATP])-tension relation to the right, and either TnI phosphorylation or partial extraction of troponin C (TnC) abolished this length-dependent shift. We conclude that TnI phosphorylation by PKA attenuates the length-dependence of tension activation in cardiac muscle by decreasing the cross-bridge-dependent thin filament activation through a reduction of the interaction between TnI and TnC.
Kajiwara
H
H
Department of Physiology (II), Jikei University School of Medicine, Tokyo, Japan. kajiwara@jikei.ac.jp
Morimoto
S
S
Fukuda
N
N
Ohtsuki
I
I
Kurihara
S
S
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D012518:Sarcomeres / Q000648:ultrastructure; D019209:Troponin C / Q000378:metabolism; D019210:Troponin I / Q000737:chemistry / Q000378:metabolism*
D019209:Troponin C; D019210:Troponin I; D000255:Adenosine Triphosphate; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium