Troponin I phosphorylation enhances crossbridge kinetics during β-adrenergic stimulation in rat cardiac tissue

Turnbull, L; Hoh, JFY; Ludowyke, RI; Rossmanith, GH

Troponin I phosphorylation enhances crossbridge kinetics during β-adrenergic stimulation in rat cardiac tissue

Turnbull, L

Hoh, JFY Ludowyke, RI Rossmanith, GH

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Publication Type:: Journal Article
Citation:: Journal of Physiology, 2002, 542 (3), pp. 911 - 920
Issue Date:: 2002-08-01

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Field	Value	Language
dc.contributor.author	Turnbull, L https://orcid.org/0000-0002-9255-9033	en_US
dc.contributor.author	Hoh, JFY	en_US
dc.contributor.author	Ludowyke, RI	en_US
dc.contributor.author	Rossmanith, GH	en_US
dc.date.issued	2002-08-01	en_US
dc.identifier.citation	Journal of Physiology, 2002, 542 (3), pp. 911 - 920	en_US
dc.identifier.issn	0022-3751	en_US
dc.identifier.uri	http://hdl.handle.net/10453/9582
dc.description.abstract	Inotropic agents that increase the intracellular levels of cAMP have been shown to increase crossbridge turnover kinetics in intact rat ventricular muscle, as measured by the parameter fmin(the frequency at which dynamic stiffness is minimum). These agents are also known to increase the level of phosphorylation of two candidate myofibrillar proteins: myosin binding protein C (MyBPC) and Troponin I (TnI), but have no effect on myosin light chain 2 phosphorylation (MyLC2). The aim of this study was to investigate whether the phosphorylation of TnI and/or MyBPC was responsible for the increase in crossbridge cycling kinetics (as captured by fmin) seen with the elevation of cAMP within cardiac tissue. Using barium-activated intact rat papillary muscle, we investigated the actions of isobutylmethylxanthine (IBMX), an inhibitor of cAMP-dependent phosphatase, which simulates the action of β-adrenergic agents, and the chemical phosphatase 2,3-butanedione monoxime (BDM), which has been shown to dephosphorylate a number of contractile proteins. The presence of 0.6 mm IBMX approximately doubled the fmin value of intact rat papillary muscle. This action was unaffected by the addition of BDM. In the presence of IBMX and BDM, the level of phosphorylation of MyBPC was unchanged, that of MyLC2 was reduced to 60% of control, yet that of TnI was markedly increased (to 30% above control levels). We conclude that TnI phosphorylation, mediated by cAMP-dependent protein kinase A, is the molecular basis for the enhanced crossbridge cycling seen during β-adrenergic stimulation of the hear.	en_US
dc.relation.ispartof	Journal of Physiology	en_US
dc.relation.isbasedon	10.1113/jphysiol.2002.022707	en_US
dc.subject.classification	Physiology	en_US
dc.subject.mesh	Myocardium	en_US
dc.subject.mesh	Papillary Muscles	en_US
dc.subject.mesh	Heart	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Rats	en_US
dc.subject.mesh	Diacetyl	en_US
dc.subject.mesh	1-Methyl-3-isobutylxanthine	en_US
dc.subject.mesh	Contractile Proteins	en_US
dc.subject.mesh	Troponin I	en_US
dc.subject.mesh	Receptors, Adrenergic, beta	en_US
dc.subject.mesh	Phosphodiesterase Inhibitors	en_US
dc.subject.mesh	Phosphorylation	en_US
dc.subject.mesh	Myocardial Contraction	en_US
dc.subject.mesh	Isometric Contraction	en_US
dc.subject.mesh	Kinetics	en_US
dc.subject.mesh	In Vitro Techniques	en_US
dc.title	Troponin I phosphorylation enhances crossbridge kinetics during β-adrenergic stimulation in rat cardiac tissue	en_US
dc.type	Journal Article
utslib.citation.volume	3	en_US
utslib.citation.volume	542	en_US
utslib.for	1108 Medical Microbiology	en_US
utslib.for	06 Biological Sciences	en_US
utslib.for	11 Medical and Health Sciences	en_US
dc.location.activity	ISI:000177609700022	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - ithree - Institute of Infection, Immunity and Innovation
utslib.copyright.status	closed_access
pubs.issue	3	en_US
pubs.publication-status	Published	en_US
pubs.volume	542	en_US

Abstract:

Inotropic agents that increase the intracellular levels of cAMP have been shown to increase crossbridge turnover kinetics in intact rat ventricular muscle, as measured by the parameter fmin(the frequency at which dynamic stiffness is minimum). These agents are also known to increase the level of phosphorylation of two candidate myofibrillar proteins: myosin binding protein C (MyBPC) and Troponin I (TnI), but have no effect on myosin light chain 2 phosphorylation (MyLC2). The aim of this study was to investigate whether the phosphorylation of TnI and/or MyBPC was responsible for the increase in crossbridge cycling kinetics (as captured by fmin) seen with the elevation of cAMP within cardiac tissue. Using barium-activated intact rat papillary muscle, we investigated the actions of isobutylmethylxanthine (IBMX), an inhibitor of cAMP-dependent phosphatase, which simulates the action of β-adrenergic agents, and the chemical phosphatase 2,3-butanedione monoxime (BDM), which has been shown to dephosphorylate a number of contractile proteins. The presence of 0.6 mm IBMX approximately doubled the fmin value of intact rat papillary muscle. This action was unaffected by the addition of BDM. In the presence of IBMX and BDM, the level of phosphorylation of MyBPC was unchanged, that of MyLC2 was reduced to 60% of control, yet that of TnI was markedly increased (to 30% above control levels). We conclude that TnI phosphorylation, mediated by cAMP-dependent protein kinase A, is the molecular basis for the enhanced crossbridge cycling seen during β-adrenergic stimulation of the hear.

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http://hdl.handle.net/10453/9582