Na ⁺ /Ca ²⁺ Exchanger

Abstract

The Na+/Ca2+ exchanger regulates intracellular calcium ([Ca2+]i), and attenuation of Na+/Ca2+ exchange by oxidative stress might lead to dysregulation of [Ca2+]i. We have shown that the Na+/Ca2+ exchanger differs functionally and at the amino acid level between salt-sensitive and salt-resistant rats. Therefore, the purpose of these studies was to determine how oxidative stress affects the activities of the 2 Na+/Ca2+ exchangers that we cloned from mesangial cells of salt-resistant (RNCX) and salt-sensitive (SNCX) Dahl/Rapp rats. The effects of oxidative stress on exchanger activity were examined in cells expressing RNCX or SNCX by assessing 45Ca2+ uptake (reverse mode) and [Ca2+]i elevation (forward mode) in the presence and absence of H2O2 and peroxynitrite. Our results showed that 45Ca2+ uptake in SNCX cells was attenuated at 500 and 750 micromol/L H2O2 (63+/-12% and 25+/-7%, respectively; n=16) and at 50 and 100 micromol/L peroxynitrite (47+/-9% and 22+/-9%, respectively; n=16). In RNCX cells, 45Ca2+ uptake was attenuated at only 750 and 100 micromol/L H2O2 and peroxynitrite (61+/-9% and 63+/-6%, respectively; n=16). In addition, the elevation in [Ca2+]i was greater in SNCX cells than in RNCX cells in response to 750 micromol/L H2O2 (58+/-5.5 vs 17+/-4.1 nmol/L; n=13) and 100 micromol/L peroxynitrite (33+/-5 vs 11+/-6 nmol/L; n=19). The enhanced impairment of SNCX activity by oxidative stress might contribute to the dysregulation of [Ca2+]i that is found in this model of salt-sensitive hypertension.

The Na⁺/Ca²⁺ Exchanger 1 (NCX1) Variant 3 as the Major Extrusion System in Renal Distal Tubular Transcellular Ca²⁺-Transport

“…NCX1.2 and NCX1.3 were described to be functional in a mouse DCT cell line; however, NCX1.7 was not expressed [14] . In another study, NCX1.3 and NCX1.7 were compared, demonstrating a difference in buffer capacity and oxidative stress response [35,36] . However, this was later partly explained by the used NCX construct, which contained a difference of one residue at position 218, which is not present in the splice region [37] .…”

In dialyzed squid axons oxidative stress inhibits the Na+/Ca2+ exchanger by impairing the Cai2+-regulatory site

“…Also, peroxynitrite inhibition of Na ϩ /Ca 2ϩ exchange activity has been reported in an in vitro preparation of microsomes from smooth muscle pulmonary artery (26) and in that of salt-sensitive hypertensive rats (50), but the sites of action were not established.…”

Attenuated renal vascular responses to acute angiotensin II infusion in smooth muscle-specific Na+/Ca2+exchanger knockout mice

“…Furthermore, arteries from smooth muscle-specific NCX1 knockout (NCX1 smϪ/Ϫ ) mice exhibit reduced Ca 2ϩ entry into vascular smooth muscle cells and reduced myogenic tone (25,35). Renovascular function plays a pivotal role in salt-dependent hypertension (9,34), and it has been reported that Na ϩ /Ca 2ϩ exchanger mechanisms are disrupted in saltsensitive hypertension (2,21,32). In contrast, other groups observed enhanced expression of NCX1 in arterial smooth muscle in several forms of hypertension (10,23,39).…”