Failure of P‐glycoprotein (MDR1) expressed in Xenopus oocytes to produce swelling‐activated chloride channel activity.

Abstract

1. P‐glycoprotein, the protein product of the multidrug resistance (MDR1) gene, has ATP‐dependent transporter activity. It has been suggested that P‐glycoprotein may also function as a volume‐regulated chloride channel or chloride channel regulator. To assess the chloride channel function of P‐glycoprotein, we examined swelling‐activated chloride conductances in Xenopus oocytes injected with human MDR1 cRNA. 2. Functional expression of P‐glycoprotein in Xenopus oocytes was confirmed using Western blot analysis and by assessing transport of the P‐glycoprotein substrate, calcein AM. 3. Endogenous, swelling‐activated chloride conductances were virtually absent by the time P‐glycoprotein expression was confirmed. Thus, this expression system afforded the advantage of assessing putative MDR1‐associated chloride currents in the absence of background currents. 4. The currents activated by hypotonic shock (50%) in both MDR1‐injected and control (water‐injected) oocytes were not significantly different. The swelling response was due in part to the activation of a potassium‐selective conductance which could be inhibited by barium. No chloride‐selective currents were activated by hypotonic shock in the presence or absence of barium. Therefore, we conclude that P‐glycoprotein expression does not produce a swelling‐activated chloride conductance in the Xenopus oocyte expression system. © 1995 The Physiological Society