The possible correlation between Pglycoprotein (PGP) and volume-sensitive Cl− channel was examined in a pair of cell lines: a subline of the human epidermoid KB cell (KB-3-1) and the corresponding MDR1-transfected cell line (KB-G2). Western blot analysis and indirect immunofluorescence studies indicated that KB-G2, but not KB-3-1, exhibits the PGP expression. Patch-clamp whole-cell recordings showed that osmotic swelling activates Cl− currents not only in PGP-expressing but also in PGP-lacking cells. The amplitude of the maximal current was indistinguishable between both cells. Activation of protein kinase C (PKC) or loading with a PKC inhibitor failed to affect the swelling-induced activation of the Cl− currents in both cells. The relation between whole-cell Cl− currents and cell size measured simultaneously showed that volume sensitivity of the Cl− channel was augmented by the PGP expression irrespective of the activity of PKC on the plasma membrane. A similar increase in volume sensitivity of the Cl− channel was also induced by the expression of the ATP hydrolysis-deficient PGP mutant, K433M. We conclude that P-glycoprotein does not represent the volume-sensitive Cl− channel but that its expression modulates volume sensitivity of the Cl− channel in a manner independent of its ATPase activity or of the protein kinase C activity.
The Journal of Membrane Biology – Springer Journals
Published: Mar 31, 2009
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