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Calcium extrusion by plasma membrane calcium pump is impaired in absence of intact caveolae
Author(s) -
ElYazbi Ahmed,
Cho Woo Jung,
Schulz Richard,
Daniel Edwin
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.916.8
Subject(s) - caveolae , plasma membrane ca2+ atpase , calcium , microbiology and biotechnology , endoplasmic reticulum , chemistry , caveolin 3 , lipid raft , biology , medicine , endocrinology , biochemistry , signal transduction , atpase , organic chemistry , enzyme
Plasma membrane calcium ATPase (PMCA) is an important calcium extrusion mechanism in smooth muscle cells with PMCA4 as the predominant isoform. PMCA is localized in lipid rafts and caveolae. In this study we examined the effects of blocking PMCA4 function in small intestinal tissue from wild type (Cav1+/+) and caveolin‐1 knockout (Cav1−/−) mice and in bovine airway smooth muscle tissue before and after caveolae disruption. Small intestinal tissues from Cav1+/+ mice treated with the PMCA4 inhibitor caloxin 1c2 (5 μM) showed a higher contractile tone to carbachol (10 μM) when compared to tissues treated with 5 μM of a control scrambled peptide. This effect of caloxin 1c2 was not seen in tissues from Cav1−/− mice. Immunohistochemistry and Western blotting showed that PMCA was co‐localized with caveolin‐1 in Cav1+/+ tissues. In bovine tracheal smooth muscle tissue, caveolae disruption by cholesterol depletion led to the diminution of caveolin‐1 and PMCA4b immunoreactivities, previously co‐localized in the smooth muscle plasma membrane, and to the loss of the increase in carbachol‐induced contraction by caloxin 1c2. Our results suggest that the calcium removal function of PMCA4 in smooth muscle cells is dependent on its presence in intact caveolae. We suggest that this is due to the close spatial arrangement that allows calcium extrusion from a privileged cytosolic space between caveolae and sarcoplasmic reticulum.