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

S P Lawrence; Geoffrey D Holman; Francoise Koumanov

doi:10.1042/bj20100717

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

S P Lawrence, Geoffrey D Holman, Francoise Koumanov

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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 language	English
Pages (from-to)	515-523
Number of pages	9
Journal	Biochemical Journal
Volume	432
Issue number	3
Early online date	23 Sept 2010
DOIs	https://doi.org/10.1042/bj20100717
Publication status	Published - 15 Dec 2010

Keywords

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

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10.1042/bj20100717

Holman_BJ_2010_432_515.pdf
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Licence: CC BY-NC

Cite this

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

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.",

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

author = "Lawrence, {S P} and Holman, {Geoffrey D} and Francoise Koumanov",

year = "2010",

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AU - Lawrence, S P

AU - Holman, Geoffrey D

AU - Koumanov, Francoise

PY - 2010/12/15

Y1 - 2010/12/15

N2 - 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.

AB - 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.

KW - glucose transporter isoform 4 (GLUT4) translocation

KW - insulin

KW - cardiomyocyte

KW - Na+/H+ exchanger 1 (NHE1) translocation

KW - cell energy status

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DO - 10.1042/bj20100717

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JO - Biochemical Journal

JF - Biochemical Journal

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Elucidation of Final Stages in Coupling of Insulin Signalling to CLUT4 Translocation

FUNCTIONAL ANALYSIS AND PATHOPHYSIOLOGY OF GLUCOSE TRANSPORT ERS

MC2-Bioimaging and cell analysis

Cite this

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Projects

Elucidation of Final Stages in Coupling of Insulin Signalling to CLUT4 Translocation

FUNCTIONAL ANALYSIS AND PATHOPHYSIOLOGY OF GLUCOSE TRANSPORT ERS

Equipment

MC2-Bioimaging and cell analysis

Cite this

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