Volume-activated chloride current is not related to P-glycoprotein overexpression.
It has been suggested that P-glycoprotein (P-gp), an ATP-dependent transporter responsible for classical multidrug resistance, is also a volume-regulated chloride channel. We reexamined this hypothesis by use of whole-cell patch clamp recordings of three matched pairs of cell lines, which were either drug-sensitive or drug-resistant due to P-gp overexpression. We demonstrate here that volume-regulated chloride-selective currents can be induced in cells with or without P-gp expression. Overexpression of either P-gp or cystic fibrosis transmembrane conductance regulator, the protein product of the CF gene and another member of the ATP-dependent transporters, is associated with a hypotonicity-induced, rapid onset, transient current prior to onset of the volume-sensitive chloride-selective current, an apparent nonspecific effect related to the overexpression of an integral membrane protein. These results suggest that there is no relationship between P-gp and the chloride channel activated by cell swelling.
Dong
Y
Y
Department of Molecular Pharmacology, Stanford University, California 94305.
Chen
K G
KG
Durán
G E
GE
Kouyama
K
K
Chao
A C
AC
Sikic
B I
BI
Gollapudi
S V
SV
Gupta
S
S
Gardner
P
P
D016475:3T3 Cells; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis*; D000818:Animals; D018118:Chloride Channels / Q000502:physiology*; D004351:Drug Resistance; D051379:Mice; D009994:Osmolar Concentration
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018118:Chloride Channels