Effect of acidosis on Ca2+ sensitivity of skinned cardiac muscle with troponin C exchange. Implications for myocardial ischemia.

By using a novel approach for the study of the effects of pH variation in skinned myocardium, the present experiments were aimed to provide new insights into the mechanism of ischemia. Ca2+ sensitivity is decreased by acid pH, but the effect is more than double in cardiac myofilaments than that in fast-twitch skeletal muscle fibers. With the technique of troponin C exchange in myocytes, we find here that the effect of pH is the same with cardiac or skeletal troponin C. These results rule out a direct H+-Ca2+ competition on the Ca2+-binding sites of troponin C as a significant mechanism of ischemia. The findings provide conclusive evidence in favor of the idea that acidosis modulates the protein-protein interactions in the regulatory complex in cardiac muscle.