P-glycoprotein is not a swelling-activated Cl- channel; possible role as a Cl- channel regulator

1. The whole-cell configuration of the patch-clamp technique was used to deter 2. Hamster pgp1 cDNA was transfected into a mouse fibroblast cell line resulting in expression of functional Pgp in the plasma membrane. This cell line was obtained without exposure to chemotherapeutic agents. 3. Swelling-activated whole-cell Cl- current (I-Cl,I-swell) was elicited by lowering the bath osmolality. I-Cl,I-swell was characterized in detail in the pgp1-transfected mouse cell line and compared with that of its parental cell line. Expression of Pgp did not modify the magnitude or properties of I-Cl,I-swell, except that addition of the anti-Pgp antibody C219 to the pipette solution inhibited this current by 75% only in the Pgp-expressing cells. 4. I-Cl,I-swell in the mouse Pgp-expressing cell line was compared with that in a Pgp-expressing hamster fibroblast cell line. The characteristics of I-Cl,I-swell (voltage dependence, blocker sensitivity, anion selectivity sequence, requirement for hydrolysable ATP) in Pgp-expressing cells were different between the two cell lines. These results suggest that the channel(s) responsible for I-Cl,I-swell are different between the two cell lines. In addition, C219 inhibited I-Cl,I-swell in both Pgp-expressing cell lines, even though they seem to express different swelling-activated Cl- channels. 5. We conclude that firstly, Pgp is not a swelling-activated Cl- channel; secondly, it possibly functions as a Cl- channel regulator; and thirdly, I-Cl,I-swell is underlined by different Cl- channels in different cells.