DRUGS TRANSPORTED BY P-GLYCOPROTEIN INHIBIT A 40PS OUTWARDLY RECTIFYING CHLORIDE CHANNEL

P-glycoprotein functions as an ATP-dependent pump for a diverse spectrum of compounds. Recently, it has been shown that P-glycoprotein may be bi-functional and act as a chloride channel as well as a pump. The single channel properties of this conductance are unknown, however, as macroscopic, whole cell currents are inhibited by substrates for P-glycoprotein transport, the single channels underlying this response should also be Mocked by these compounds. We found that colchicine, vinblastine, daunomycin and verapamil (50 mu M) caused block of a 40 pS outwardly-rectifying chloride channel in cells expressing P-glycoprotein. The inhibitory effect of these compounds appeared specific for the 40 pS chloride channel as a large, 300 pS chloride channel found in the same cells was unaffected by addition of drug. These results suggest that the 40 pS chloride channel may be associated with P-glycoprotein expression. (C) 1994 Academic Press, Inc.