Reduced troponin I phosphorylation and increased Ca(2+)-dependent ATP-consumption in triton X-skinned fiber preparations from Galphaq overexpressor mice.

Overexpression of the Galphaq-protein has been shown to result in hypertrophic and dilated cardiomyopathy. This study investigated Ca(2+ )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 Galphaq-protein (Galphaq-OE; n = 11). In addition, the phosphorylation status of troponin I was measured. Ca(2+) sensitivity of tension was increased in Galphaq-OE with a significant reduction in the half-maximum Ca(2+) concentration (EC(50)) compared to WT. Similarly, Ca(2+) sensitivity of myosin ATPase activity was increased in Galphaq-OE when comparing Galphaq-OE to WT. Maximum Ca(2+)-dependent tension and ATPase activity were both enhanced in Galphaq-OE compared to WT littermates. Phosphorylation of troponin I was significantly reduced in Galphaq-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 Galphaq-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 Galphaq-OE.
AuthorsC Pott, L Willkomm, S Grafweg, B Bölck, G W Dorn 2nd, R H G Schwinger, K Brixius
JournalMolecular and cellular biochemistry (Mol Cell Biochem) Vol. 314 Issue 1-2 Pg. 133-41 (Jul 2008) ISSN: 0300-8177 [Print] Netherlands
PMID18473122 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Keratolytic Agents
  • Troponin I
  • Adenosine Triphosphate
  • Octoxynol
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Calcium
  • Adenosine Triphosphate (metabolism)
  • Animals
  • Calcium (pharmacology)
  • Calcium Signaling (drug effects)
  • Female
  • GTP-Binding Protein alpha Subunits, Gq-G11 (genetics)
  • Keratolytic Agents (pharmacology)
  • Male
  • Mice
  • Mice, Transgenic
  • Muscle Contraction (drug effects)
  • Muscle Fibers, Skeletal (drug effects, metabolism)
  • Octoxynol (pharmacology)
  • Phosphorylation (drug effects)
  • Troponin I (metabolism)
  • Up-Regulation

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