ABNORMAL CHLORIDE CONDUCTANCE IN MULTIDRUG RESISTANT HL60/AR CELLS

被引:17
作者
GOLLAPUDI, S
MCDONALD, T
GARDNER, P
KANG, N
GUPTA, S
机构
[1] UNIV CALIF IRVINE,DIV BASIC & CLIN IMMUNOL,ROOM C-264A,IRVINE,CA 92717
[2] STANFORD UNIV,FALK CARDIOVASC RES CTR,SCH MED,DEPT MED,STANFORD,CA 94305
关键词
MULTIDRUG RESISTANCE; INTRACELLULAR PH; CHLORIDE CURRENT;
D O I
10.1016/0304-3835(92)90284-3
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Chloride channel currents were measured in drug sensitive parental HL60 and multidrug resistant (MDR) subline HL60/AR cells, using a whole cell patch-clamp technique. In addition, the in vitro effects of 4,4'diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), a Cl- channel blocker, on intracellular accumulation and sensitivity to daunorubicin and intracellular pH (pH(i)) in HL60 cells were examined. Baseline DIDS blockable Cl- currents were consistently lower in HL60/AR cells (0.9 pA/pF) as compared to HL60 cells (7.0 pA/pF). Similarly cAMP-activated Cl- currents were minimal in HL60/AR cells (0.2 pA/pF) as compared to HL60 cells (8 pA/pF). In vitro treatment of drug sensitive HL60 cells with DIDS resulted in concentration-dependent decreased accumulation and increased resistance to daunorubicin and decreased pH(i). These data show that altered Cl- permeability is associated with MDR and suggest that Cl- channels may play a role in MDR.
引用
收藏
页码:83 / 89
页数:7
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