Purified endogenous inhibitor of the Na/Ca exchanger can enhance the cardiomyocytes contractility and calcium transients

Previous studies have shown that the newly found endogenous inhibitor (NCXIF) of the cardiac Na/Ca exchanger (NCX1) is capable of regulating the muscle strip’s contractility and relaxation. Here, the effects of purified NCXIF were tested on single cell shortening–lengthening (by using the IR CCD camera coupled with the two-edge video-detector) and [Ca]i-transients (by monitoring the changes in fluo-3 fluorescence). A perfusion of isolated cardiomyocytes (paced at 0.5–1.0 Hz) with NCXIF results in 4–6-fold enhancement in the amplitude of cell shortening–lengthening reaching the steady-state levels within 5–8 min (n = 20, p < 0.009). Simultaneous recordings of cell shortening–lengthening and [Ca]i-transients from the same cell show that the amplitude enhancement is associated with accelerated decay of both signals. Therefore, the NCXIF-dependent modulation of the single cell contractility is primarily governed by Ca-related mechanisms. The observed data are consistent with a proposal suggesting that the inhibition of NCX1 by NCXIF results in Ca-dependent activation of SERCA (SR Ca ATPase), yielding the accelerated decay of the [Ca]i-transients. The subsequent increase in the SR Ca content may result in enhanced Ca-release reflecting the manifested promotion of [Ca]i-transients. More systematic study is required for confirming this working hypothesis.