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 (NCX(IF)) of the cardiac Na/Ca exchanger (NCX1) is capable of regulating the muscle strip's contractility and relaxation. Here, the effects of purified NCX(IF) 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 NCX(IF) 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 NCX(IF)-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 NCX(IF) 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.
Liron
Boyman
B
Department of Physiology and Pharmacology, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv 69978, Israel.
Reuben
Hiller
H
Beni
Shpak
S
Chagit
Shpak
S
Khananshvili
Daniel
D
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004594:Electrophysiology; D006168:Guinea Pigs; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D011817:Rabbits; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors* / Q000378:metabolism
D019831:Sodium-Calcium Exchanger; D002118:Calcium