FAILURE OF P-GLYCOPROTEIN (MDR1) EXPRESSED IN XENOPUS OOCYTES TO PRODUCE SWELLING-ACTIVATED CHLORIDE CHANNEL ACTIVITY

1. P-glycoprotein, the protein product of the multidrug resistance (MD R1) gene, has ATP-dependent transporter activity. It has been suggeste d 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 c onductances in Xenopus oocytes injected with human MDR1 cRNA. 2. Funct ional expression of P-glycoprotein in Xenopus oocytes was confirmed us ing Western blot analysis and by assessing transport of the P-glycopro tein substrate, calcein AM. 3. Endogenous, swelling-activated chloride conductances were virtually absent by the time P-glycoprotein express ion was confirmed. Thus, this expression system afforded the advantage of assessing putative MDR1-associated chloride currents in the absenc e of background currents. 4. The currents activated by hypotonic shock (50 %) in both MDR1-injected and control (water-injected) oocytes wer e not significantly different. The swelling response was due in part t o the activation of a potassium-selective conductance which could be i nhibited by barium. No chloride-selective currents were activated by h ypotonic shock in the presence or absence of barium. Therefore, we con clude that P-glycoprotein expression does not produce a swelling-activ ated chloride conductance in the Xenopus oocyte expression system.