Troponin I phosphorylation in spontaneously hypertensive rat heart: effect of beta-adrenergic stimulation.
We compared baseline and protein kinase A (PKA)-dependent troponin I (TnI) phosphorylation in 32Pi-labeled left ventricular myocytes from hearts of 26-wk spontaneously hypertensive rats (SHR) and Wistar-Kyoto controls (WKY). TnI phosphorylation was normalized to myosin light chain 2 phosphorylation, which was invariant. There was no difference in baseline TnI phosphorylation in SHR and WKY, but stimulation with isoproterenol, norepinephrine plus prazosin, forskolin, chloroadenosine 3',5'-cyclic monophosphate, or 3-isobutyl-1-methylxanthine caused a greater increase in TnI phosphorylation in the SHR than in the WKY. This was observed both in the presence and absence of the phosphatase inhibitor calyculin A; thus the differences in TnI phosphorylation between SHR and WKY are not due to decreased phosphatase activity in the SHR. After stimulation of the beta-adrenergic pathway, phospholamban phosphorylation was not different in SHR and WKY, indicating that the observed differences may be specific for PKA phosphorylation of TnI. The increased PKA-dependent TnI phosphorylation in the SHR resulted in decreased Ca2+ sensitivity of actomyosin adenosinetriphosphatase activity as compared with the WKY. We conclude that increased PKA-dependent TnI phosphorylation in the SHR may contribute to the impaired response to sympathetic stimulation.
McConnell
B K
BK
Department of Molecular Cardiology, Cleveland Clinic Foundation 44195, USA.
Moravec
C S
CS
Morano
I
I
Bond
M
M
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006352:Heart Ventricles; D006973:Hypertension / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008387:Marine Toxins; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D019210:Troponin I / Q000378:metabolism*; D000099211:Phospholamban
D015056:1-Methyl-3-isobutylxanthine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000318:Adrenergic beta-Agonists; D002118:Calcium; D002135:Calcium-Binding Proteins; D005576:Colforsin; D017868:Cyclic AMP-Dependent Protein Kinases; D004791:Enzyme Inhibitors; D007545:Isoproterenol; D008387:Marine Toxins; D018994:Myosin Light Chains; D009638:Norepinephrine; D010080:Oxazoles; D010749:Phosphoprotein Phosphatases; D011224:Prazosin; D019210:Troponin I; D000099211:Phospholamban; C059041:calyculin A; C044258:8-chloro-cyclic adenosine monophosphate