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.
Pott
C
C
Department of Cardiology and Angiology, Hospital of the University of Münster, Munster, Germany.
Willkomm
L
L
Grafweg
S
S
Bölck
B
B
Dorn
G W
GW
Schwinger
R H G
RH
Brixius
K
K
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects; D005260:Female; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics*; D007641:Keratolytic Agents / Q000494:pharmacology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009119:Muscle Contraction / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D017830:Octoxynol / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D019210:Troponin I / Q000378:metabolism*; D015854:Up-Regulation
D007641:Keratolytic Agents; D019210:Troponin I; D000255:Adenosine Triphosphate; D017830:Octoxynol; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D002118:Calcium