Towards Understanding the Role of the Na(+)-Ca (2+) Exchanger Isoform 3.

Towards Understanding the Role of the Na(+)-Ca (2+) Exchanger Isoform 3. Rev Physiol Biochem Pharmacol. 2015 Apr 8; Authors: Michel LY, Hoenderop JG, Bindels RJ Abstract The Na(+)-Ca(2+) exchanger (NCX) is critical for Ca(2+) homeostasis throughout the body. Of the three isoforms in the NCX family, NCX1 has been extensively studied, providing a good basis for understanding the molecular aspects of the NCX family, including structural resemblances, stoichiometry, and mechanism of exchange. However, the tissue expression of the third isoform of the family, NCX3, together with its proposed involvement in the Ca(2+) fluxes of the endoplasmic reticulum and the mitochondria suggests a distinctive role for this isoform. Investigations of the exchanger revealed the involvement of NCX3 in diverse processes such as bone formation, TNF-α production, slow-twitch muscle contraction, and long-term potentiation in the hippocampus. Furthermore, the study of its posttranslational modification, its cleavage by the Ca(2+)-sensitive protease, calpain, and its upregulation in numerous stress conditions linked NCX3 to the aberrant Ca(2+) influx seen during neuronal excitotoxicity in Alzheimer's disease, brain stroke, and neuronal injuries. Hence, beyond its role in calcium homeostasis, NCX3 plays an important role in stress conditions, neuronal excitotoxicity, and metabolism and is thereby a key element in many cell types. The present review aims to surv...
Source: Pharmacological Reviews - Category: Drugs & Pharmacology Authors: Tags: Rev Physiol Biochem Pharmacol Source Type: research