Mechanisms of Na+-Ca2+ exchange inhibition by amphiphiles in cardiac myocytes: importance of transbilayer movement

The Journal of Membrane Biology
M KellerM Egger

Abstract

The membrane lipid environment and lipid signaling pathways are potentially involved in the modulation of the activity of the cardiac Na(+)-Ca(2+) exchanger (NCX). In the present study biophysical mechanisms of interactions of amphiphiles with the NCX and the functional consequences were examined. For this purpose, intracellular Ca(2+) concentration jumps were generated by laser-flash photolysis of caged Ca(2+) in guinea-pig ventricular myocytes and Na(+)-Ca(2+) exchange currents ( I(Na/Ca)) were recorded in the whole-cell configuration of the patch-clamp technique. The inhibitory effect of amphiphiles increased with the length of the aliphatic chain between C(7) and C(10) and was more potent with cationic or anionic head groups than with uncharged head groups. Long-chain cationic amines (C(12)) exhibited a cut-off in their efficacy in I(Na/Ca) inhibition. Analysis of the time-course, comparison with the Ni(2+)-induced I(Na/Ca) block and confocal laser scanning microscopy experiments with fluorescent lipid analogs (C(6)- and C(12)-NBD-labeled analogs) suggested that amphiphiles need to be incorporated into the membrane. Furthermore, NCX block appears to require transbilayer movement of the amphiphile to the inner leaflet ("flip...Continue Reading

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Feb 14, 2006·British Journal of Pharmacology·Christophe PignierBruno Le Grand
Nov 12, 2015·World Journal of Gastroenterology : WJG·Luis Ruiz-del-Árbol, Regina Serradilla

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