CHLORIDE CHANNELS ACTIVATED BY OSMOTIC-STRESS IN T-LYMPHOCYTES

被引:199
|
作者
LEWIS, RS [1 ]
ROSS, PE [1 ]
CAHALAN, MD [1 ]
机构
[1] UNIV CALIF IRVINE,DEPT PHYSIOL & BIOPHYS,IRVINE,CA 92717
来源
JOURNAL OF GENERAL PHYSIOLOGY | 1993年 / 101卷 / 06期
关键词
D O I
10.1085/jgp.101.6.801
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
We have used whole-cell and perforated-patch recording techniques to characterize volume-sensitive Cl- channels in T and B lymphocytes. Positive transmembrane osmotic pressure (intracellular osmolality > extracellular osmolality) triggers the slow induction of a Cl- conductance. Membrane stretch caused by cellular swelling may underlie the activation mechanism, as moderate suction applied to the pipette interior can reversibly oppose the induction of Cl- current by an osmotic stimulus. Intracellular ATP is required for sustaining the Cl- current. With ATP-free internal solutions, the inducibility of Cl- current declines within minutes of whole-cell recording, while in.whole-cell recordings with ATP or in perforated-patch experiments, the current can be activated for at least 30 min. The channels are anion selective with a permeability sequence of I- > SCN- > NO3-, Br- > Cl- > MeSO3- > acetate, propionate > ascorbate > aspartate and gluconate. G(Cl) does not show voltage- and time-dependent gating behavior at potentials between - 100 and + 100 mV, but exhibits moderate outward rectification in symmetrical Cl- solutions. Fluctuation analysis indicates a unitary chord conductance of approximately 2 pS at - 80 mV in the presence of symmetrical 160 mM Cl-. The relationship of mean current to current variance during the osmotic activation of Cl- current implies that each cell contains on the order of 10(4) activatable Cl- channels, making it the most abundant ion channel in lymphocytes yet described. The current is blocked in a voltage-dependent manner by DIDS and SITS (K(i) = 17 and 89 muM, respectively, at + 40 mV), the degree of blockade increasing with membrane depolarization. The biophysical and pharmacological properties of this Cl- channel are consistent with a role in triggering volume regulation in lymphocytes exposed to hyposmotic conditions.
引用
收藏
页码:801 / 826
页数:26
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