Interaction of the Na+-Ca2+ exchanger with small molecules on cell Ca2+ signaling

Interactions of the Na+-Ca2+ exchanger with small molecules on cell Ca2+ signaling were elucidated in Chinese hamster ovary (CHO) C1 cells, which transfected a control vector without any expression of the Na+-Ca2+ exchangerʹs gene while CHO CK1.4 cells transfected an expression vector encoding the bovine cardiac Na+-Ca2+ exchangerʹs cDNA, treated with lithiumor sodium-buffer medium respectively, by using L16(2)15 multifactorial orthogonal statistics and fura-2 fluorescence real-time imaging. In contrast to controls of Li+-treated C1 cells, the store-dependent Ca2+-influx (SDCI) was enhanced by either the Na+-Ca2+ exchanger, Na+, 1-β-[3-(4-methoxyphenyl)propoxy¦-4-methoxyphenethyl-1H-imidazole HCl (SK&F96365) or ouabain, and by interactions of the Na+-Ca2+ exchanger with either Na+, SK&F96365 or both SK&F96365 and ouabain; and ATP-induced Ca2+ release (AICR) was activated by SK&F96365 or Na+ alone, interactions of the Na+-Ca2+ exchanger with SK&F96365 or Na+, and an interaction between SK&F96365 and ouabain. The dramatic interaction of the Na+-Ca2+ exchanger with small molecules indicates that cell Ca2+ signaling is generated by inositol triphosphate (InsP3)-dependent pathways, allosteric effects of the G-protein coupled P2y&2u purinoceptor and multisite recognition. Our findings provide meaningful clues for designing new strategies of cardiocerebral vascular oxidative diseases.