Macula densa cell signaling involves ATP release through a maxi anion channel
Macula densa cell signaling involves ATP release through a maxi anion channel
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DOI：
10.1073/pnas.0736323100
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发表时间：
2003-04-01
影响因子：
11.1
通讯作者：
Okada, Y
中科院分区：
文献类型：
--
作者：
Bell, PD;Lapointe, JY;Okada, Y
致密斑细胞是独特的肾脏生物传感器细胞，其检测管腔NaCl浓度（[NaCl]L）的变化并将信号传递到系膜细胞/传入小动脉复合体。它们是肾脏水盐排泄和肾小球血流动力学之间的重要联系，因此在体液容量的调节中起关键作用。自20世纪初发现这些细胞以来，从致密斑细胞到肾小球收缩元件的信号传导过程的性质仍然未知。在致密斑细胞的膜片钳研究中，我们确定了一个[NaCl] L-敏感的ATP可渗透的大电导（380 pS）阴离子通道。此外，我们直接证明了释放ATP（高达10 μ M）在致密斑细胞的基底外侧膜，在依赖于[NaCl]L的方式，通过使用ATP生物测定技术。此外，我们发现，肾小球系膜细胞的反应与升高胞浆呼叫浓度的ATP（EC 50 0.8 μ M）的细胞外应用。重要的是，我们还发现，当fura-2加载的系膜细胞被放置在致密斑细胞的基底外侧膜附近时，胞浆Ca（2+）浓度随着[NaCl]L升高而增加。因此，表达P2 Y（2）受体的致密斑细胞和系膜细胞之间的细胞间通讯涉及通过基底外侧膜上的最大阴离子通道从致密斑细胞释放ATP。这一机制可能代表了ATP介导的细胞间信号转导的新范式。
Macula densa cells are unique renal biosensor cells that detect changes in luminal NaCl concentration ([NaCl]L) and transmit signals to the mesangial cell/afferent arteriolar complex. They are the critical link between renal salt and water excretion and glomerular hemodynamics, thus playing a key role in regulation of body fluid volume. Since identification of these cells in the early 1900s, the nature of the signaling process from macula densa cells to the glomerular contractile elements has remained unknown. In patch-clamp studies of macula densa cells, we identified an [NaCl]L-sensitive ATP-permeable large-conductance (380 pS) anion channel. Also, we directly demonstrated the release of ATP (up to 10 muM) at the basolateral membrane of macula densa cells, in a manner dependent on [NaCl]L, by using an ATP bioassay technique. Furthermore, we found that glomerular mesangial cells respond with elevations in cytosolic Call concentration to extracellular application of ATP (EC50 0.8 muM). Importantly, we also found increases in cytosolic Ca (2+) concentration with elevations in [NaCl]L, when fura-2-loaded mesangial cells were placed close to the basolateral membrane of macula densa cells. Thus, cell-to-cell communication between macula densa cells and mesangial cells, which express P2Y(2) receptors, involves the release of ATP from macula densa cells via maxi anion channels at the basolateral membrane. This mechanism may represent a new paradigm in cell-to-cell signal transduction mediated by ATP.