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Review
. 1996 Jul;9(7):703-7.
doi: 10.1016/0895-7061(95)00447-5.

The links between cellular Ca2+ and Na+/H+ exchange in the pathophysiology of essential hypertension

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Review

The links between cellular Ca2+ and Na+/H+ exchange in the pathophysiology of essential hypertension

A Aviv. Am J Hypertens. 1996 Jul.

Abstract

This review focuses on the mechanisms whereby the cytosolic Ca2+ regulates the ubiquitous Na+/ H+ exchanger (NHE-1) and how these regulatory processes might modify the behavior of NHE-1 in essential hypertension. The pH setpoint for activation of the Na+/H+ exchanger is controlled by two interrelated and Ca(2+)-dependent pathways, namely, the protein kinase/ phosphatase cascade and Ca2+/calmodulin. The cytoplasmic domain of NHE-1 contains elements responsive to serine/theorine kinases and a high affinity binding site to Ca2+/calmodulin. Phosphorylation of NHE-1 or the binding of the Ca2+/calmodulin complex to its binding site promotes an alkaline shift in the pH setpoint for the exchanger. It is suggested that, in essential hypertension, an increased cellular Ca2+ load or an enhanced external Ca2+ entry stimulate the NHE-1 through protein kinase/phosphatase and Ca2+/calmodulin systems, thereby increasing its activity.

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