The Sodium Pump and Cardiotonic Steroids-induced Signal Transduction Protein Kinases and Calcium-signaling Microdomain in Regulation of Transporter Trafficking

Document Type

Article

Publication Date

2010

Abstract

The Na/K-ATPase was discovered as an energy transducing ion pump. A major difference between the Na/K-ATPase and other P-type ATPases is its ability to bind a group of chemicals called cardiotonic steroids (CTS). The plant-derived CTS such as digoxin are valuable drugs for the management of cardiac diseases, whereas ouabain and marinobufagenin (MBG) have been identified as a new class of endogenous hormones. Recent studies have demonstrated that the endogenous CTS are important regulators of renal Na+ excretion and blood pressure. The Na/K-ATPase is not only an ion pump, but also an important receptor that can transduce the ligand-like effect of CTS on intracellular protein kinases and Ca2+ signaling. Significantly, these CTS-provoked signaling events are capable of reducing the surface expression of apical NHE3 (Na/H exchanger isoform 3) and basolateral Na/K-ATPase in renal proximal tubular cells. These findings suggest that endogenous CTS may play an important role in regulation of tubular Na+ excretion under physiological conditions; conversely, a defect at either the receptor level (Na/K-ATPase) or receptor–effector coupling would reduce the ability of renal proximal tubular cells to excrete Na+, thus culminating/resulting in salt-sensitive hypertension.

Comments

Open Access to this review article is provided by Elsevier. The Elsevier user license is found at http://www.elsevier.com/about/open-access/open-access-policies/oa-license-policy/elsevier-user-license. Copyright © 2010 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.bbadis.2010.01.013

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