Calcium wave of tubuloglomerular feedback
Calcium wave of tubuloglomerular feedback
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DOI：
10.1152/ajprenal.00425.2005
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发表时间：
2006-08-01
影响因子：
4.2
通讯作者：
Peti-Peterdi, Janos
中科院分区：
文献类型：
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作者：
Peti-Peterdi, Janos
致密黄斑(MD)细胞向肾小球旁装置(JGA)间质释放的ATP是控制肾小球滤过率的肾小管球反馈(TGF)机制的重要组成部分。由于JGA的细胞表达许多钙偶联的嘌呤能受体，这些研究验证了这样的假设，即转化生长因子的激活触发了从MD向JGA和肾小球的远端细胞扩散的钙波。用Fluo-4/Fura Red和共聚焦荧光显微镜对体外微灌流分离的兔JGA-肾小球复合体进行了比值钙成像。在MD，通过增加肾小管流量来激活转化生长因子，使肾小球系膜外细胞内钙离子浓度([Ca~(2+)](I))显著升高(增加187.6+/-45.1nM)和JG肾素颗粒细胞(增加281.4+/-66.6nM)。随后，观察到钙信号以12.6+/-1.1µm/S的速率向上游传入小动脉近段和邻近肾小球，以及向包括最远的足细胞在内的肾小球内成分传播(5.9+/-0.4µm/S)。在非灌注性肾小球中也观察到同样的钙波，引起血管收缩和肾小球束的收缩。缝隙连接解偶联和药物抑制P-2嘌呤能受体，但不阻断腺苷A(1)受体，可消除[Ca~(2+)](I)的变化和钙波的传播。这些研究证明，缝隙连接通讯和细胞外ATP都是转化生长因子钙波的组成部分。
ATP release from macula densa ( MD) cells into the interstitium of the juxtaglomerular (JG) apparatus (JGA) is an integral component of the tubuloglomerular feedback (TGF) mechanism that controls the glomerular filtration rate. Because the cells of the JGA express a number of calcium-coupled purinergic receptors, these studies tested the hypothesis that TGF activation triggers a calcium wave that spreads from the MD toward distant cells of the JGA and glomerulus. Ratiometric calcium imaging of in vitro microperfused isolated JGA-glomerulus complex dissected from rabbits was performed with fluo-4/fura red and confocal fluorescence microscopy. Activation of TGF by increasing tubular flow rate at the MD rapidly produced a significant elevation in intracellular Ca2+ concentration ([Ca2+](i)) in extraglomerular mesangial cells (by 187.6 +/- 45.1 nM) and JG renin granular cells (by 281.4 +/- 66.6 nM). Subsequently, cell-to-cell propagation of the calcium signal at a rate of 12.6 +/- 1.1 mu m/s was observed upstream toward proximal segments of the afferent arteriole and adjacent glomeruli, as well as toward intraglomerular elements including the most distant podocytes (5.9 +/- 0.4 mu m/s). The same calcium wave was observed in nonperfusing glomeruli, causing vasoconstriction and contractions of the glomerular tuft. Gap junction uncoupling, an ATP scavenger enzyme cocktail, and pharmacological inhibition of P-2 purinergic receptors, but not adenosine A(1) receptor blockade, abolished the changes in [Ca2+](i) and propagation of the calcium wave. These studies provided evidence that both gap junctional communication and extracellular ATP are integral components of the TGF calcium wave.