A mechanism of Ca2+ release from Ca2+ stores coupling to the Na+/Ca2+ exchanger in cultured smooth muscle cells

We previously observed Ca2+ release from intracellular Call stores caused b y reduction in extracellular Na+ concentration ([Na+](o)) (1). The purpose of this study was to determine whether lowering [Na+](o) can elicit Ca2+ re lease from Ca2+ stores via the Na+/Ca2+ exchanger and to elucidate the mech anisms related to the Ca2+ release pathway in cultured longitudinal smooth muscle cells obtained from zn guinea pig ileum. Low [Na+](o)-induced Ca2+ r elease was inhibited by antisense oligodeoxynucleotides for Na+/Ca2+ exchan ger type I (anti-NCX). Application of anti-NCX to cells attenuated both the number of Ca2+ responding cells and the expression of the exchanger. Moreo ver, microinjection of heparin, a blocker of inositol. 1,4,5-trisphosphate (IP3) receptors, into the cells inhibited low [Na+](o)-induced Ca2+ release . These findings suggest that low [Na+](o)-induced Call release occurs thro ugh an IP3-induced Ca2+ release mechanism due to changes in the Ca2+ flux r egulated by the Na+/Ca2+ exchanger. (C) 2001 Elsevier Science Inc. All righ ts reserved.