This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vaughan-Jones, R. D. Articles by Swietach, P. Search for Related Content PubMed PubMed Citation Articles by Vaughan-Jones, R. D. Articles by Swietach, P. Related Collections Related Article

(Circulation Research. 2008;103:773.)
© 2008 American Heart Association, Inc.

Editorials

Pushing and Pulling the Cardiac Sodium/Hydrogen Exchanger

Richard D. Vaughan-Jones, Pawel Swietach

From the Burdon Sanderson Cardiac Science Centre, Department of Physiology, Anatomy and Genetics, Oxford, United Kingdom.

Correspondence to Richard D. Vaughan-Jones, Department of Physiology, Anatomy and Genetics, Burdon Sanderson Cardiac Science Center, Parks Rd, Oxford OX1 3PT, United Kingdom. E-mail richard.vaughan-jones@dpag.ox.ac.uk

See related article, pages 881–890

Key Words: pH_i • NHE1 • PKB/Akt • hypertrophy • ischemia

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The strangest animal in Dr Dolittle’s zoo was a Pushmi-pullyu (pronounced push-me-pull-you), a mythical chimera of 2 antelopes, with a head at each end. Sometimes it looked and moved forwards, sometimes backwards. The direction could be coaxed by Dr Dolittle (played originally by Rex Harrison in the Hollywood movie), who spoke to the animal in its own language. A report from the laboratory of Avkiran, published in this issue of Circulation Research,¹ shows that there is something strangely reminiscent of the Pushmi-pullyu in the cardiac sodium–hydrogen exchanger (NHE1), a ubiquitous, dimeric glycoprotein, intimately involved with the regulation of intracellular pH (pH_i) (reviewed elsewhere²). In cardiac myocytes, the NHE1 protein product is expressed at the sarcolemma. It is a secondary active transporter expelling one H⁺ ion in exchange for the entry of one Na⁺ ion, and its activity is governed acutely by the intracellular H⁺ ion concentration (ie, pH_i). Activity increases steeply when pH_i falls from its resting level of 7.2. This is why the protein is so effective as a pH_i regulator.

But why the resemblance to a Pushmi-pullyu? It is becoming apparent that NHE1 in the cardiac cell can be both stimulated and inhibited directly by intracellular signaling cascades. Like Dr Dolittle, these talk to the transporter, and the chorus determines whether cellular H⁺ extrusion during intracellular acidosis is stimulated or inhibited. It has long been known that the pH_i sensitivity of NHE1 can be enhanced through a coupling of the transport protein to surface . . . [Full Text of this Article]

Related Article:

Protein Kinase B/Akt Phosphorylates and Inhibits the Cardiac Na^+/H⁺ Exchanger NHE1

Andrew K. Snabaitis, Friederike Cuello, and Metin Avkiran
Circ. Res. 2008 103: 881-890. [Abstract] [Full Text] [PDF]

This article has been cited by other articles:

				O. H. Cingolani, N. G. Perez, and H. E. Cingolani Letter by Cingolani et al Regarding Article, "Ventricular Phosphodiesterase-5 Expression Is Increased in Patients With Advanced Heart Failure and Contributes to Adverse Ventricular Remodeling After Myocardial Infarction in Mice" Circulation, October 13, 2009; 120(15): e137 - e137. [Full Text] [PDF]

				A. Darmellah, C. Rucker-Martin, and D. Feuvray ERM proteins mediate the effects of Na+/H+ exchanger (NHE1) activation in cardiac myocytes Cardiovasc Res, February 1, 2009; 81(2): 294 - 300. [Abstract] [Full Text] [PDF]