CVIC Lab.CardioVascular-Ion Channel Laboratory

Despite distinctive functional and anatomic differences, a precise understanding of the cardiac interventricular differences in excitation–contraction (E–C) coupling mechanisms is still lacking. Here, we directly compared rat right and left cardiomyocytes (RVCM and LVCM). Whole-cell patch clamp, the IonOptix system, and fura-2 fluorimetry were used to measure electrical properties (action potential and ionic currents), single-cell contractility, and cytosolic Ca²⁺ ([Ca²⁺]_i), respectively. Myofilament proteins were analyzed by immunoblotting. RVCM showed significantly shorter action potential duration (APD) and higher density of transient outward K⁺ current (I_to). However, the triggered [Ca²⁺]_i change (Ca²⁺ transient) was not different, while the decay rate of the Ca²⁺ transient was slower in RVCM. Although the relaxation speed was also slower, the sarcomere shortening amplitude (ΔSL) was smaller in RVCM. SERCA activity was ∼60% lower in RVCM, which is partly responsible for the slower decay of the Ca²⁺ transient. Immunoblot analysis revealed lower expression of the cardiac troponin complex (cTn) in RVCM, implying a smaller Ca²⁺ buffering capacity (κ_S), which was proved by in situ analysis. The introduction of these new levels of cTn, I_to, and SERCA into a mathematical model of rat LVCM reproduced the similar Ca²⁺ transient, slower Ca²⁺ decay, shorter APD, and smaller ΔSL of RVCM. Taken together, these data show reduced expression of cTn proteins in the RVCM, which provides an explanation for the interventricular difference in the E–C coupling kinetics.