ATP released from Astrocytes during swelling activates chloride channels
ATP released from Astrocytes during swelling activates chloride channels
复制标题
DOI：
10.1152/jn.00510.2002
复制
发表时间：
2003-04-01
影响因子：
2.5
通讯作者：
MacVicar, BA
中科院分区：
文献类型：
--
作者：
Darby, M;Kuzmiski, JB;MacVicar, BA
从星形胶质细胞释放ATP有助于钙（[Ca 2 +]）波传播，并可能调节神经元兴奋性。在上皮细胞和肝细胞中，细胞肿胀导致ATP释放，这导致通过涉及嘌呤能受体的自分泌途径激活体积敏感性Cl-电流（I-Cl，I-溶胀）。星形胶质细胞肿胀通过调节性体积减少来平衡，涉及代谢物的流出和I-Cl、I-肿胀和K+电流的激活。应用全细胞膜片钳技术研究了ATP在低渗溶液（HOS）激活星形胶质细胞I-Cl、I-swell中的自分泌作用。腺苷三磷酸双磷酸酶是一种ATP/ADP核苷酸酶，它抑制HOS激活的I-Cl，I-swell，而ATP和P2 Y激动剂ADP β S和ADP则诱导类似于I-Cl，I-swell的Cl-电流。P2 U激动剂UTP和P2 X激动剂α，β-亚甲基ATP都无效。BzATP的作用不如ATP，表明P2 X7受体不参与。P2嘌呤能拮抗剂苏拉明、RB 2和磷酸吡哆醛-6-偶氮苯-2 '，4'-二磺酸（PPADS）可逆地抑制I-Cl，I-swell的激活，提示ATP激活P2 Y1受体。因此ATP释放通过激活P2 Y1样受体介导星形胶质细胞中的I-Cl，I-溶胀。多药耐药蛋白（MRP）转运抑制剂丙磺舒、吲哚美辛和MK-571均有效抑制I-Cl、I-肿胀。使用荧光素酶直接观察到HOS中星形胶质细胞的ATP释放，MK-571可逆地抑制这种HOS诱导的ATP流出。我们的结论是ATP释放通过MRP和随后的自分泌激活的嘌呤能受体有助于激活的I-Cl，I-肿胀的星形胶质细胞由HOS诱导的肿胀。
ATP release from astrocytes contributes to calcium ([Ca2+]) wave propagation and may modulate neuronal excitability. In epithelial cells and hepatocytes, cell swelling causes ATP release, which leads to the activation of a volume-sensitive Cl- current (I-Cl,I- swell) through an autocrine pathway involving purinergic receptors. Astrocyte swelling is counterbalanced by a regulatory volume decrease, involving efflux of metabolites and activation of I-Cl,I- swell and K+ currents. We used whole cell patch-clamp recordings in cultured astrocytes to investigate the autocrine role of ATP in the activation of I-Cl,I- swell by hypo-osmotic solution (HOS). Apyrase, an ATP/ADP nucleotidase, inhibited HOS-activated I-Cl,I- swell, whereas ATP and the P2Y agonists, ADPbetaS and ADP, induced Cl- currents similar to I-Cl,I- swell. Neither the P2U agonist, UTP nor the P2X agonist, alpha,beta-methylene ATP, were effective. BzATP was less effective than ATP, suggesting that P2X7 receptors were not involved. P2 purinergic antagonists, suramin, RB2, and pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid ( PPADS) reversibly inhibited activation of I-Cl,I- swell, suggesting that ATP-activated P2Y1 receptors. Thus ATP release mediates I-Cl,I- swell in astrocytes through the activation of P2Y1-like receptors. The multidrug resistance protein (MRP) transport inhibitors probenicid, indomethacin, and MK-571 all potently inhibited I-Cl,I- swell. ATP release from astrocytes in HOS was observed directly using luciferin-luciferase and MK-571 reversibly depressed this HOS-induced ATP efflux. We conclude that ATP release via MRP and subsequent autocrine activation of purinergic receptors contributes to the activation of I-Cl,I- swell in astrocytes by HOS-induced swelling.