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

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.