High impact information on SLC8A2

• The three Na+/Ca2+ exchanger isoforms, NCX1, NCX2, and NCX3, contain a large cytoplasmic loop that is responsible for the regulation of activity [1].
• Cloning of the NCX2 isoform of the plasma membrane Na(+)-Ca2+ exchanger [2].
• Transcripts of NCX2 are detected in brain and skeletal muscle [2].
• The genes for NCX1 and NCX2 are located on human chromosomes 2 and 14, respectively [2].
• NCX2 was expressed in Xenopus oocytes and Na(+)-Ca2+ exchange activity was analyzed electrophysiologically by the giant inside-out, excised patch technique [2].

Biological context of SLC8A2

• We now report the cloning of a second isoform (NCX2) of the Na(+)-Ca2+ exchanger which was present in a rat brain cDNA library [2].
• Both NCX1 and NCX2 feature an unusual 1.8-kb exon, containing two-thirds of the protein coding sequence and a similar area of the coding sequences split into several small exons, displaying tissue-specific alternative splicing [3].
• By contrast, one splicing variant of the isoform PMCA4 and one of the Na/Ca exchangers of the plasma membrane (NCX2) become very rapidly down-regulated: Their down-regulation is also controlled by calcineurin [4].
• The remainder of the NCX1 (NCX2) gene, coding for a putative cytoplasmic regulatory domain, is split into 9 (7) small exons [5].
• The Na(+)/Ca(2+) exchanger gene family encompasses three distinct proteins, NCX1, NCX2, and NCX3, which mediate cellular Ca(2+) efflux and thus contribute to intracellular Ca(2+) homeostasis [6].

Anatomical context of SLC8A2

• In this study we investigated the time-related alteration of gene and protein expressions of NCX1, NCX2, and NCX3 in rat brain cortex after 2 h of transient middle cerebral artery occlusion (tMCAO) [7].
• RT-PCR showed NCX1 expression in both HeLa and NCTC cell lines and also NCX2 in the latter; NCX3, a subtype previously observed in NG108-15 cells, was not expressed in either [8].

Associations of SLC8A2 with chemical compounds

• On the other hand, the isothiourea derivative KB-R7943 was threefold more inhibitory to NCX3 than to NCX1 or NCX2 [9].
• Ni2+ inhibited 45Ca2+ uptake by competing with Ca2+ for the external transport site, with 10-fold less affinity in NCX3 than in NCX1 or NCX2 [9].

References