title: The links between cellular Ca2+ and Na+/H+ exchange in the pathophysiology of essential hypertension.
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.
authors.affiliation: Hypertension Research Program, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103-2714, USA.
authors.forename: A
authors.initials: A
authors.lastname: Aviv
mesh_terms: D002118:Calcium / Q000502:physiology*; D002147:Calmodulin / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D011494:Protein Kinases / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*
chemical_list: D002147:Calmodulin; D017923:Sodium-Hydrogen Exchangers; D011494:Protein Kinases; D002118:Calcium