Reduced troponin I phosphorylation and increased Ca2+- dependent ATP-consumption in triton X-skinned fiber preparations from Gαq overexpressor mice

C. Pott, L. Willkomm, S. Grafweg, B. Böck, G. W. Dorn, R. H.G. Schwinger, K. Brixius

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Overexpression of the Gαq-protein has been shown to result in hypertrophic and dilated cardiomyopathy. This study investigated Ca2+ sensitivity of tension and myosin-ATPase activity in skinned fiber preparations of male and female wildtype (WT; n = 12) and transgenic mice with a cardiac specific overexpression of the Gαq-protein (Gαq-OE; n = 11). In addition, the phosphorylation status of troponin I was measured. Ca2+ sensitivity of tension was increased in Gαq-OE with a significant reduction in the half-maximum Ca2+ concentration (EC50) compared to WT. Similarly, Ca2+ sensitivity of myosin ATPase activity was increased in Gαq-OE when comparing Gαq-OE to WT. Maximum Ca2+-dependent tension and ATPase activity were both enhanced in Gαq-OE compared to WT littermates. Phosphorylation of troponin I was significantly reduced in Gαq-OE compared to WT. In the above experiments, no gender specific differences were observed in either Gaq-OE or in WT. We conclude that, in mice, increased expression of the Gαq-protein induces alterations of myofibrillar function and energy consumption, which are also characteristics of human heart failure. This may result from a decreased phosphorylation of troponin I in Gαq-OE.

Original languageEnglish
Pages (from-to)133-141
Number of pages9
JournalMolecular and Cellular Biochemistry
Volume314
Issue number1-2
DOIs
StatePublished - Jul 1 2008
Externally publishedYes

Keywords

  • Ca sensitivity
  • Gαq
  • Heart failure
  • Myocardium
  • Myosin ATPase
  • Transgenic mice
  • Troponin
  • β-Adrenergic signaling

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