Pallone Thomas L, Cao Chunhua, Zhang Zhong
Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201-1595, USA.
Am J Physiol Renal Physiol. 2004 Dec;287(6):F1213-22. doi: 10.1152/ajprenal.00241.2004. Epub 2004 Aug 17.
We tested whether K(+) channel inhibition accompanies ANG II-induced depolarization of descending vasa recta (DVR) pericytes. An increase in extracellular K(+) concentration (K(+)) from 5 to 100 mM depolarized resting pericytes but had no effect after prolonged (10 nM, 20 min) ANG II exposure. In contrast, reduction of extracellular Cl(-) concentration (Cl(-)) from 154 to 34 mM had a minor effect on resting membrane potential but strongly depolarized pericytes treated with ANG II. The K(+) channel blockers BaCl(2) (0.1, 1 mM) and tetraethylammonium (TEA; 30 mM) depolarized resting pericytes but did not affect membrane potential of ANG II-treated pericytes. Pericyte whole cell currents were reduced by ANG II and nearly eliminated by combined ANG II exposure and the Cl(-) channel blocker niflumic acid (100 muM). Augmentation of inward current induced by raising K(+) from 5 to 50 mM was eliminated by preexposure to ANG II. TEA- and BaCl(2)-sensitive outward currents, generated by depolarizing pericytes from -80 to -40 mV, were eliminated by ANG II. We conclude that ANG II depolarizes DVR pericytes by a combination of Cl(-) channel activation and K(+) channel inhibition.
我们测试了血管紧张素II（ANG II）诱导的降支直小血管（DVR）周细胞去极化过程中是否伴随着钾离子通道抑制。细胞外钾离子浓度（[K⁺]ₒ）从5 mM增加到100 mM会使静息周细胞去极化，但在长时间（10 nM，20分钟）暴露于ANG II后没有影响。相反，细胞外氯离子浓度（[Cl⁻]ₒ）从154 mM降低到34 mM对静息膜电位影响较小，但会使经ANG II处理的周细胞强烈去极化。钾离子通道阻滞剂氯化钡（0.1 mM、1 mM）和四乙铵（TEA；30 mM）会使静息周细胞去极化，但不影响经ANG II处理的周细胞的膜电位。ANG II会降低周细胞全细胞电流，而联合暴露于ANG II和氯离子通道阻滞剂氟尼酸（100 μM）几乎可消除该电流。预先暴露于ANG II可消除将[K⁺]ₒ从5 mM提高到50 mM所诱导的内向电流增加。将周细胞从 -80 mV去极化到 -40 mV所产生的对TEA和氯化钡敏感的外向电流被ANG II消除。我们得出结论，ANG II通过激活氯离子通道和抑制钾离子通道的组合使DVR周细胞去极化。
