Translocation of the Na+/H+ exchanger 1 (NHE1) in cardiomyocyte responses to insulin and energy-status signalling

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Abstract

The Na+/H+ exchanger NHE1 is a highly regulated membrane protein that is required for pH homoeostasis in cardiomyocytes. The activation of NHE1 leads to proton extrusion, which is essential for counteracting cellular acidity that occurs following increased metabolic activity or ischaemia. The activation of NHE1 intrinsic catalytic activity has been well characterized and established experimentally. However, we have examined in the present study whether a net translocation of NHE1 to the sarcolemma of cardiomyocytes may also be involved in the activation process. We have determined the distribution of NHE1 by means of immunofluorescence microscopy and cell-surface biotinylation. We have discovered changes in the distribution of NHE1 that occur when cardiomyocytes are stimulated with insulin that are PI3K (phosphoinositide 3-kinase)-dependent. Translocation of NHE1 also occurs when cardiomyocytes are challenged by hypoxia, or inhibition of mitochondrial oxidative metabolism or electrically induced contraction, but these responses occur through a PI3K-independent process.
Original languageEnglish
Pages (from-to)515-523
Number of pages9
JournalBiochemical Journal
Volume432
Issue number3
Early online date23 Sep 2010
DOIs
Publication statusPublished - 15 Dec 2010

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Cardiac Myocytes
Chemical activation
Insulin
Phosphatidylinositols
1-Phosphatidylinositol 4-Kinase
Phosphotransferases
Enzyme inhibition
Sodium-Hydrogen Antiporter
Biotinylation
Metabolism
Acidity
Sarcolemma
Extrusion
Protons
Catalyst activity
Microscopic examination
Membrane Proteins
Fluorescence Microscopy
Homeostasis
Ischemia

Keywords

  • glucose transporter isoform 4 (GLUT4) translocation
  • insulin
  • cardiomyocyte
  • Na+/H+ exchanger 1 (NHE1) translocation
  • cell energy status

Cite this

Translocation of the Na+/H+ exchanger 1 (NHE1) in cardiomyocyte responses to insulin and energy-status signalling. / Lawrence, S P; Holman, Geoffrey D; Koumanov, Francoise.

In: Biochemical Journal, Vol. 432, No. 3, 15.12.2010, p. 515-523.

Research output: Contribution to journalArticle

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