ATP-activated chloride channel inhibited by an antibody to P glycoprotein

Abstract

In this report, we present the characteristics of a Cl- channel found in lens fiber cells. The single channel has a conductance of 17 pS, a linear current-voltage curve, is activated by ATP or strong depolarization and is blocked by verapamil, quinidine, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, 5-nitro-2-(3- phenylpropylamino)benzoate, dideoxyforskolin, and tamoxifen. These properties are similar to those reported for a volume-activated Cl- channel associated with the multidrug resistance (MDR) gene product, P glycoprotein (24). Confirming this connection, we demonstrate that our lens Cl- channel is inhibited by an antibody to P glycoprotein. The data we present here may, therefore, be the first characterization of the single channel activity of the Cl- channel associated with P glycoprotein.