Discordant interventricular differences in the excitation‐contraction coupling explained by the lower levels of troponin and Ca ²⁺ buffering in the right ventricle of rats

Abstract

The left and right ventricles have distinctive functional characteristics as well as the anatomical differences. However, precise understanding of interventricular differences in the excitation‐contraction (E‐C) coupling mechanisms and the Ca2+ homeostasis is still lacking. Here we compared the results from the right and left cardiomyocytes (RVCMs and LVCMs) of rats by using whole‐cell patch clamp and IonOptix measuring cytosolic Ca2+ ([Ca2+]i) and contractility. RVCMs showed significantly shorter action potential duration (APD), with higher density of transient outward K+ current (Ito) while similar L‐type Ca2+ current. However, the triggered [Ca2+]ichange (Ca2+ transient) was not different while the decaying rate of Ca2+ transient was slower in RVCMs. More perplexingly, the sarcomere shortening amplitude (DSL) was smaller and the relaxation speed was slower in RVCMs than LVCMs. The analysis of SERCA activity in situ revealed approximately 50% lower level in RVCMs. Interestingly, the immunoblot analysis revealed lower expression of cardiac troponin complex (cTnC, cTnI and cTnT) in RVCMs. The lower Ca2+ binding cTnC implied smaller Ca2+ buffering capacity (κS), which could be responsible for the similar amplitude of Ca2+‐transient despite the shorter APD in RVCMs. In situ analysis using known concentration of fura‐2 revealed lower κS in the RVCMs. Introduction of the 1.9 fold Ito, 0.5 fold SERCA, and 0.7 fold cTn into the mathematical model of rat LVCM reproduced the similar Ca2+ transient and the slower Ca2+ decay along with the shorter APD of RVCM. Taken together, we firstly show the lower expression of cTn proteins in the RVCMs, which gives a clue to explain the inter‐ventricular difference in the E‐C coupling kinetics.