Angiotensin II depolarizes podocytes in the intact glomerulus of the rat
Angiotensin II depolarizes podocytes in the intact glomerulus of the rat
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DOI：
10.1172/jci119467
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发表时间：
1997-06-01
影响因子：
15.9
通讯作者：
Pavenstadt, H
中科院分区：
文献类型：
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作者：
Gloy, J;Henger, A;Pavenstadt, H
本研究的目的是研究血管紧张素II（Ang II）对大鼠足细胞（POD）在完整的新鲜分离的肾小球和培养的细胞功能的影响。用膜片钳技术分别测定了快速全细胞和全细胞制霉菌素模式下豆荚的膜电压（Vm）和离子电流。V-m为-38+/-1mV（n = 86），Ang Ⅱ使pod发生浓度依赖性去极化，ED_（50）为10（-8）mol/L。在血管紧张素Ⅱ（10（-7）摩尔/升，n = 20）的存在下，pod去极化7+/-1 mV。在Cl-浓度降低至32 mmol/L的细胞外溶液中，Ang IT对V-m的作用显著增加至14+/-4 mV（n = 8）。由血管紧张素II诱导的去极化既不抑制在细胞外Na+-自由的解决方案，也不与减少细胞外Ca 2+（降至1 μ mol/L）的解决方案。与血管紧张素II一样，钙离子载体A23187（10（-5）mol/L，n = 9）使豆荚去极化10+/-2 mV，而毛喉素（10（-5）mol/L）、8-（4-氯苯硫基）-cAMP和N2，2 '-o-二丁酰-cGMP（均为5 × 10（-4）mol/L）不改变豆荚的V-m。血管紧张素1受体拮抗剂losartan（10（-7）mol/L）可完全抑制Ang Ⅱ（10（-7）mol/L）诱导的去极化（n = 5）。与肾小球中的pod一样，短期培养的pod对Ang II（10（-8）mol/L，n = 5）有去极化反应。我们的研究结果表明，血管紧张素II去极化足细胞直接开放的Cl-电导。这种离子电导的激活是由AT（1）受体介导的，并可能受到细胞内Ca 2+活性的调节。
The aim of this study was to examine the effects of angiotensin II (Ang II) on cellular functions of rat podocytes (pod) in the intact freshly isolated glomerulus and in culture. Membrane voltage (V-m) and ion currents of pod were examined with the patch clamp technique in fast whole cell and whole cell nystatin configuration. V-m of pod was -38+/-1 mV (n = 86), Ang II led to a concentration-dependent depolarization of pod with an ED50 of 10(-8) mol/liter. In the presence of Ang II (10(-7) mol/liter, n = 20), pod depolarized by 7+/-1 mV. In an extracellular solution with a reduced Cl- concentration of 32 mmol/liter, the effect of Ang IT on V-m was significantly increased to 14+/-4 mV (n = 8). The depolarization induced by Ang II was neither inhibited in an extracellular Na+-free solution nor in a solution with a reduced extracellular Ca2+ (down to 1 mu mol/liter). Like Ang II, the calcium ionophore A23187 (10(-5) mol/liter, n = 9) depolarized pod by 10+/-2 mV, whereas forskolin (10(-5) mol/liter), 8-(4-chlorophenylthio)-cAMP and N2,2'-o-dibutyryl-cGMP (both 5 x 10(-4) mol/liter) did not alter V-m of pod. The angiotensin 1 receptor antagonist losartan (10(-7) mol/liter) completely inhibited the Ang II-induced (10(-7) mol/liter) depolarization (n = 5). Like pod in the glomerulus, pod in short term culture depolarized in response to Ang II (10(-8) mol/liter, n = 5). Our results suggest that Ang II depolarizes podocytes directly by opening a Cl- conductance. The activation of this ion conductance is mediated by an AT(1) receptor and may be regulated by the intracellular Ca2+ activity.