Elsevier Inc. Stim1 Na+ ---> Na+ in (3) Mcu complex Ca2+ outside ---> Ca2+ Ca2+ Ca2+ ---> Ca2+ stored Ca2+ stored ---> Ca2+ released Na+ ---> Na+ in (4) calcium/calcium-mediated signaling pathway RYRs ITPRs NCKXs NCXs PMCAs ROCs ORAIs CNGs TRPs VOCs NAADP cADPr IP3 Ca2+ outside Ca2+ ---> CA2+ pumped out Ca2+ exchanged CA2+ pumped out Atp2c2 Tpcn2 ---> Ca2+ released Tpcn1 ---> Ca2+ released Ca2+ stored ORAIs ---- Stim2 Ca2+ ---- ITPRs IP3 ---- ITPRs ORAIs ---- Stim1 Na+ Ca2+ ---- RYRs Na+ in (3) Na+ in (4) cADPr ---- RYRs NAADP ---- Tpcn1 NAADP ---- Tpcn2 Mcoln1 ---> Ca2+ released Ca2+ released Atp2c1 Tpcn1 Tpcn2 Mcoln1 Stim2 Slc24a6 Ca2+ ---> Ca2+ exchanged Stim1 --+> ORAIs SERCAs