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Regulation of Ca 2+ Signaling by Na + Pump Alpha‐2 Subunit Expression
Author(s) -
GOLOVINA VERA,
SONG HONG,
JAMES PAUL,
LINGREL JERRY,
BLAUSTEIN MORDECAI
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2003.tb07236.x
Subject(s) - alpha (finance) , protein subunit , chemistry , physics , radiochemistry , biochemistry , psychology , gene , clinical psychology , construct validity , psychometrics
A bstract : The role of the Na + pump α2 subunit in Ca 2+ signaling was examined in primary cultured astrocytes from wild type (WT) mouse fetuses and those with a null mutation in one (Het) or both (KO) α2 genes. Cytosol Na + and Ca 2+ concentrations ([Na + ] CYT and [Ca 2+ ] CYT ) were measured with benzofuran isophthalate (SBFI) and Fura‐2. Het astrocytes express ∼50% of normal α2; KO cells express none. Resting [Na + ] CYT = 6.5 mM in WT, 6.8 mM in Het, and 8.0 mM in KO cells; 500 nM ouabain (which inhibits only α2) equalized [Na + ] CYT at 8 mM in all genotypes. Resting [Ca 2+ ] CYT = 132 nM in WT, 162 nM in Het and 196 nM in KO cells. Cyclopiazonic acid (CPA), which inhibits endoplasmic reticulum (ER) Ca 2+ pumps, induces elevation of [Ca 2+ ]CYT. These Ca 2+ responses are augmented in Het and KO cells. This correlates with α2 Na + pump and Na + /Ca 2+ exchanger (NCX) localization in plasma membrane (PM) microdomains that overlie the ER. Selective reduction of α2 Na + pump activity apparently elevates local [Na + ] and, via NCX, [Ca 2+ ] in the tiny cytosolic space between the PM and ER. This augments adjacent ER Ca 2+ stores and amplifies Ca 2+ signaling without elevating bulk [Na + ] CYT .