Receptor-Mediated Regulation of the Cardiac Sarcolemmal Na+/H+ Exchanger

Mechanisms And (Patho)Physiological Significance
  • Robert S. Haworth
  • Metin Avkiran

Abstract

Intracellular pH (pHi) homeostasis in cardiac myocytes is achieved principally by the integrated action of 4 different sarcolemmal ion transporters (1). When the myocyte cytoplasm becomes acidic, the Na+/H+ exchanger (NHE) and the Na+/HCO3 - cotransporter (NBC) extrude acid from the cell, while under conditions of intracellular alkalosis, the Cl-/HCO3 - and Cl-/OH- exchangers effectively import acid. In order to investigate the function and regulation of NHE, experimental protocols are often performed in the absence of bicarbonate, which renders NBC inactive and thereby makes NHE the sole acid extrusion pathway. NHE activity is regulated primarily by pHi, and increases markedly in response to intracellular acidosis (1) through the interaction of H+ with an allosteric modifier site on the transport domain (2,3). The basal activity of the sarcolemmal NHE is low under physiological conditions, while increasing intracellular acidosis leads to a pHi-dependent increase in NHE activity, with a Hill coefficient of around 3 (4). This indicates that more than 1 proton binds to the NHE protein during the transport cycle, and has led to the suggestion that the NHE protein contains a non-transporting proton-binding site which allosterically modifies NHE activity. Thus, as pHi falls, the proton modifier site becomes increasingly occupied, leading to a greater increase in NHE activity than would be expected by simply in creasing the availability of transportable protons.

Keywords

Ischemia Adenosine Angiotensin Catecholamine Cardiol 

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Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Robert S. Haworth
    • 1
  • Metin Avkiran
    • 1
  1. 1.Centre for Cardiovascular Biology and Medicine, King’s College London, The Rayne InstituteSt Thomas’ HospitalLondonUK

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