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

P-glycoprotein functions as an ATP-dependent pump for a diverse spectr um of compounds. Recently, it has been shown that P-glycoprotein may b e bi-functional and act as a chloride channel as well as a pump. The s ingle channel properties of this conductance are unknown, however, as macroscopic, whole cell currents are inhibited by substrates for P-gly coprotein transport, the single channels underlying this response shou ld also be Mocked by these compounds. We found that colchicine, vinbla stine, daunomycin and verapamil (50 mu M) caused block of a 40 pS outw ardly-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 s ame cells was unaffected by addition of drug. These results suggest th at the 40 pS chloride channel may be associated with P-glycoprotein ex pression. (C) 1994 Academic Press, Inc.