Caveolin-1 modulates the activity of the volume-regulated chloride channel

1. Caveolae are small invaginations of the plasma membrane that have recent ly been implicated in signal transduction. In the present study, we have in vestigated whether caveolins, the principal protein of caveolae, also modul ate volume-regulated anion channels (VRBCs). 2. I-Cl,I-swell, the cell swelling-induced chloride current through VRACs, was studied in three caveolin-1-deficient cell lines: Caco-2, MCF-7 and T47 D. 3. Electrophysiological measurements showed that I-Cl,I-swell was very smal l in these cells and that transient expression of caveolin-1 restored I-Cl, I-swell. The caveolin-1. effect was isoform specific: caveolin-1 beta but n ot caveolin-1 alpha: upregulated VRACs. This correlated with a different su bcellular distribution of caveolin-1 alpha (perinuclear location) from cave olin-1 beta (perinuclear and peripheral). 4. To explain the modulation of I-Cl,I-swell by caveolin-1 we propose that caveolin increases the availability of VRACs in the plasma membrane or, alt ernatively, that it plays a crucial role in the signal transduction cascade of VRACs.