Mutual regulatory mechanism between Ca2+ permeable receptors and channels and Ca2+ binding proteins

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We reported that the expression of Ca2+ binding proteins, calbindin-D28k (CB) and parvalbumin correlates with the expression of Ca2+ permeable AMPA receptors (AMPA-Rs) in rat forebrain. We analyzed cell surface expression of a Ca2+ impermeable subunit, GluR2 and a Ca2+ permeable subunit, GluR2Q using an adenoviral-mediated expression system in COS7 cells. Biochemical measurements of cell surface expressed subunits using biotinylation experiments revealed that cell surface expression of GluR2Q is significantly increased with CB coexpression. By application of AMPA-R blockers, cell surface expression of GluR2Q is increased in the absence of CB coexpression. To determine whether Ca2+ entry via Ca2+ permeable AMPA receptor causes the suppression, we used the Ca2+ chelater, BAPTA-AM. Application of BAPTA-AM increases cell surface expression of GluR2Q. These results suggest that CB enhances cell surface expression of Ca2+ permeable AMPA-Rs by buffering the increased intracellular Ca2+ that enters through Ca2+ permeable AMPA-Rs.