Rapid interaction of FRCRCFa with the cytosolic side of the cardiac sarcolemma Na(+)-Ca2+ exchanger blocks the ion transport without preventing the binding of either sodium or calcium

Biochemistry
D KhananshviliB Mester

Abstract

Positively charged cyclic hexapeptide Phe-Arg-Cys-Arg-Cys-Phe-CONH2 (FRCRCFa) represents a group of conformationally constrained peptides that block the cardiac sarcolemma Na(+)-Ca2+ exchanger [Khananshvili et al. (1995b) J. Biol. Chem. 270, 16182-16188]. Here, we study the kinetic mechanisms of FRCRCFa-induced inhibition of Na(+)-Ca2+ exchange and its partial reaction, the Ca(2+)-Ca2+ exchange. The Nai-dependent 45Ca uptake and Cai-dependent 45Ca uptake were measured by adding the EGTA quench in the semirapid mixer. The reverse mode of Na(+)-Ca2+ exchange (Nao-dependent Ca efflux) was monitored (t = 10-5000 ms) in the stopped-flow machine by measuring extravesicular free calcium with a fluorescence probe fluo-3. Saturating concentrations of FRCRCFa inhibit completely the forward and reverse modes of exchange, suggesting that the inside-out vesicles contribute to most (if not all) of the exchange activity. A short time exposure (t = 10-20 ms) of FRCRCFa with the vesicles is enough to reach a rapid equilibrium between FRCRCFa and a putative inhibitory site at the extravesicular (cytosolic) side of the membrane. A lower limit for the second-order rate constant of FRCRCFa binding can be estimated as a kon of > 10(6) M-1 s-1. A pos...Continue Reading

References

Jan 1, 1991·Annals of the New York Academy of Sciences·D Khananshvili
Sep 1, 1982·The American Journal of Physiology·K D Philipson, A Y Nishimoto
Jul 7, 1995·The Journal of Biological Chemistry·D KhananshviliD Baazov
Apr 15, 1996·Annals of the New York Academy of Sciences·K D PhilipsonJ N Weiss
Apr 15, 1996·Annals of the New York Academy of Sciences·D A NicollK D Philipson

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Citations

Jul 1, 2010·The Journal of Biological Chemistry·Moshe GiladiDaniel Khananshvili
Oct 12, 2000·Biochemical and Biophysical Research Communications·R HillerD Khananshvili
Jul 2, 2003·Expert Opinion on Investigational Drugs·Sheila A Doggrell, Jules C Hancox
Oct 27, 2004·Biochemical and Biophysical Research Communications·Chagit ShpakDaniel Khananshvili
Oct 18, 2005·Biochemical and Biophysical Research Communications·Liron BoymanDaniel Khananshvili
Aug 2, 2003·Biochemical and Biophysical Research Communications·Chagit ShpakDaniel Khananshvili
Dec 17, 2004·Pharmacological Reviews·L AnnunziatoG F Di Renzo
Jul 3, 1999·Physiological Reviews·M P Blaustein, W J Lederer

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