Expression of drosophila melanogaster p-glycoproteins is associated with atp-channel activity. Bosch, Irene, George R. Jackson, Jr., James M. Croop, and Horacio F. Cantiello. Division of Pediatric Hematology/Oncology, Dana Farber Cancer Institute, and The Children's Hospital, Renal Unit, Massachusetts General Hospital East, and Department of Medicine, Harvard Medical School
APStracts 3:0203C, 1996.
Two distinct Drosophila melanogaster P-glycoprotein (Pgp) gene homologs of different chromosomal origin, MDR49 and MDR65, have been previously identified (38). Most Pgps are implicated in the development of the multidrug-resistance phenotype. Despite intense efforts to identify the molecular mechanism(s) associated with Pgp function, the endogenous substrate(s) of these transport molecules is(are), largely unknown. Recent studies from our laboratory indicate that a murine Pgp homolog (1), and a related protein, the cystic fibrosis transmembrane conductance regulator (CFTR (25)) are novel ATP-permeable ion channels. The common feature of these two proteins is the conserved ATP-binding cassettes (ABC), thus molecules structurally linked to the ABC transporter family may be also functionally associated with ATP channel activity. In this study, MDR65 and MDR49 Pgs were functionally expressed in Sf9 cells, and patch-clamp techniques were applied to assess the role of these proteins in the electrodiffusional movement of ATP. In the presence of intracellular ATP and external NaCl, expression of MDR65 was associated with a linear electrodiffusional pathway that was permeable to both ATP and Cl-. Under symmetrical ATP conditions, only voltage depolarization activated a MDR65-mediated ATP-conductive pathway. Expression of MDR49 was also associated with a voltage -activated ATP conductance in symmetrical ATP but no apparent permeability to either Cl- or ATP was observed under asymmetrical conditions. The different functional properties of MDR65 and MDR49 may be indicative of distinct physiological roles in this organism. The study indicates, however, that the two Drosophila P-glycoprotein homologs share strong functional similarities with their mammalian relatives Pgp and CFTR. 

Received 21 September 1995; accepted in final form 24 May 1996.
APS Manuscript Number C572-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 July 96