TY - JOUR
T1 - Purified endogenous inhibitor of the Na/Ca exchanger can enhance the cardiomyocytes contractility and calcium transients
AU - Liron, Boyman
AU - Reuben, Hiller
AU - Beni, Shpak
AU - Chagit, Shpak
AU - Khananshvili, Daniel
N1 - Funding Information:
We are grateful to Drs. W.P. Lederer and B. Stedman for expert advice for measuring the [Ca] i -transients and cell shortening–lengthening in our laboratory. This work was supported in part by the Israeli Academy of Sciences (Grant #16.0-424) and the USA-Israeli Binational Science foundation, BSF (Grant #2003-372).
PY - 2006/8/4
Y1 - 2006/8/4
N2 - 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.
AB - 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.
KW - Calcium
KW - Calcium transient
KW - Cardiomyocyte
KW - EC-coupling
KW - Endogenous inhibitor
KW - SERCA
KW - Sodium-calcium exchange
UR - http://www.scopus.com/inward/record.url?scp=33745203480&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2006.06.020
DO - 10.1016/j.bbrc.2006.06.020
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C2 - 16782052
AN - SCOPUS:33745203480
SN - 0006-291X
VL - 346
SP - 1100
EP - 1107
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -