PT  - JOURNAL ARTICLE
AU  - V. Sathish
AU  - A.J. Abcejo
AU  - M.A. Thompson
AU  - G.C. Sieck
AU  - Y.S. Prakash
AU  - C.M. Pabelick
TI  - Caveolin-1 regulation of store-operated Ca<sup>2+</sup> influx in human airway smooth muscle
AID  - 10.1183/09031936.00090511
DP  - 2012 Jan 01
TA  - European Respiratory Journal
PG  - erj00905-2011
4099  - http://erj.ersjournals.com/content/early/2012/01/12/09031936.00090511.short
4100  - http://erj.ersjournals.com/content/early/2012/01/12/09031936.00090511.full
AB  - Caveolae, plasma membrane invaginations with constitutive caveolin proteins, harbour proteins involved in intracellular calcium ([Ca2+]i) regulation. In human airway smooth muscle (ASM), store-operated Ca2+ entry (SOCE) is a key component of [Ca2+]i regulation, and contributes to increased [Ca2+]i in inflammation. SOCE involves proteins Orai1 and stromal interaction molecule 1 (STIM1). We investigated the link between caveolae, SOCE and inflammation in ASM.[Ca2+]i was measured in human ASM cells using fura-2. siRNA or overexpression vectors were used to alter expression of caveolin-1 (Cav-1), Orai1 or STIM1. TNFα was used as a representative pro-inflammatory cytokine.TNFα increased SOCE following sarcoplasmic reticulum Ca2+ depletion, and increased whole-cell and caveolar Orai1 (but only intracellular STIM1). Cav-1 siRNA decreased caveolar and whole cell Orai1 (but not STIM1) expression, and blunted SOCE, even in the presence of TNFα. STIM1 overexpression substantially enhanced SOCE: an effect only partially reversed by Cav-1 siRNA. In contrast, Orai1 siRNA substantially blunted SOCE even in the presence of TNFα. Cav-1 overexpression significantly increased Orai1 expression and SOCE, especially in the presence of TNFα.These results demonstrate that caveolar expression and regulation of proteins such as Orai1 are important for [Ca2+]i regulation in human ASM cells and its modulation during inflammation.