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Review
. 2010 Dec;1802(12):1237-45.
doi: 10.1016/j.bbadis.2010.01.013. Epub 2010 Feb 6.

The sodium pump and cardiotonic steroids-induced signal transduction protein kinases and calcium-signaling microdomain in regulation of transporter trafficking

Jiang Liu  1 , Zi-Jian Xie
Affiliations
Review

The sodium pump and cardiotonic steroids-induced signal transduction protein kinases and calcium-signaling microdomain in regulation of transporter trafficking

Jiang Liu et al. Biochim Biophys Acta. 2010 Dec.

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 Ca(2+) 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.

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Figures

Figure 1
Figure 1
Schematic presentation of ouabain-induced regulation of basolateral Na/K-ATPase and apical NHE3 in renal proximal tubule cells. NKA, Na/K-ATPase.
See this image and copyright information in PMC

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