Selective activation of SERCA2a preserves tension during acidosis in mouse myocardium

Abstract

It is well known that intracellular Ca²⁺ regulates cardiac muscle contraction and cardiac Ca²⁺ ATPase of sarcoplasmic reticulum (SERCA2a) plays a dominant role in Ca²⁺ handling. During acidosis, peak tension decreases, although the peak of the Ca²⁺ transient (CaT) increases, which could be due to a decrease in the Ca²⁺ sensitivity of the myofilaments. We hypothesized that an increase in the SERCA2a activity delivers more Ca²⁺ to the contractile elements and diminishes the decrease in tension during acidosis. In order to prove the hypothesis, we used the aequorin method and measured tension with CaT in left ventricular papillary muscles obtained from the transgenic mouse (TG) which overexpresses cardiac-restricted SERCA2a (almost doubled) and from the non-transgenic littermates (NTG). The peaks of CaT and tension in TG were larger than those in NTG in the control solution. In CO₂ (15%) acidosis, tension decreased to 25% of the control in NTG and decreased to 50% in TG. During recovery from acidosis, tension did not reach the control level in NTG but fully recovered in TG. During acidosis and recovery phase, the peak of CaT in TG was significantly larger than that in NTG. These results suggest that the increased activity of SERCA2a could be beneficial to preserve tension during acidosis and recovery by delivering suffcient Ca²⁺ to the myofilaments. [Jpn J Physiol 54 Suppl:S97 (2004)]