Modulation of Ca super(2+) Signaling by Na super(+)/Ca super(2+) Exchangers in Mast Cells

• Published in: The Journal of immunology (1950) 2005-01, Vol.174 (1), p.119-130
• Main Authors: Aneiros, Eduardo, Philipp, Stephan, Lis, Annette, Freichel, Marc, Cavalie, Adolfo
• Format: Article
• Language: English
• ISSN: 0022-1767

Mast cells rely on Ca super(2+) signaling to initiate activation programs leading to release of proinflammatory mediators. The interplay between Ca super(2+) release from internal stores and Ca super(2+) entry through store-operated Ca super(2+) channels has been extensively studied. Using rat basophilic leukemia (RBL) mast cells and murine bone marrow-derived mast cells, we examine the role of Na super(+)/Ca super(2+) exchangers. Calcium imaging experiments and patch clamp current recordings revealed both K super(+)-independent and K super(+)-dependent components of Na super(+)/Ca super(2+) exchange. Northern blot analysis indicated the predominant expression of the K super(+)-dependent sodium-calcium exchanger NCKX3. Transcripts of the exchangers NCX3 and NCKX1 were additionally detected in RBL cells with RT-PCR. The Ca super(2+) clearance via Na super(+)/Ca super(2+) exchange represented [approx]50% of the total clearance when Ca super(2+) signals reached levels =>200 nM. Ca super(2+) signaling and store-operated Ca super(2+) entry were strongly reduced by inverting the direction of Na super(+)/Ca super(2+) exchange, indicating that Na super(+)/Ca super(2+) exchangers normally extrude Ca super(2+) ions from cytosol and prevent the Ca super(2+)-dependent inactivation of store-operated Ca super(2+) channels. Working in the Ca super(2+) efflux mode, Na super(+)/Ca super(2+) exchangers such as NCKX3 and NCX3 might, therefore, play a role in the Ag-induced mast cell activation by controlling the sustained phase of Ca super(2+) mobilization.