Adenosine stimulates depolarization and rise in cytoplasmic [Ca2+] in type I cells of rat carotid bodies
Adenosine stimulates depolarization and rise in cytoplasmic [Ca2+] in type I cells of rat carotid bodies
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DOI：
10.1152/ajpcell.00546.2005
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发表时间：
2006-06-01
影响因子：
5.5
通讯作者：
Tse, A
中科院分区：
文献类型：
--
作者：
Xu, FL;Xu, JH;Tse, A
在缺氧期间，由于ATP催化和腺苷通过腺苷转运体流出，颈动脉体中的腺苷水平增加。使用钙离子成像，我们发现腺苷，通过A（2A）受体，触发了大鼠颈动脉体的I型（血管球）细胞胞浆[Ca 2 +]（[Ca 2 +]（i））的上升。腺苷的反应可以模仿毛喉素（但不是其无活性的类似物），并可以取消PKA抑制剂H89。同时测量膜电位（穿孔膜片记录）和[Ca 2 +]（i）表明腺苷介导的[Ca 2 +]（i）升高伴随着去极化。电压门控性钙通道（VGCC）阻断剂Ni ~（2+）可阻断腺苷介导的[Ca ~（2+）]（i）升高。虽然腺苷被报道抑制4-氨基吡啶（4-AP）敏感的K+电流，4-AP未能触发任何[Ca 2 +]（i）的上升，或减弱腺苷的反应。与此相反，大麻素，一种TWIK相关的酸敏感性K+-1（TASK-1）通道的抑制剂，触发去极化和[Ca 2 +]（i）升高。腺苷反应衰减anandamide，但不是由四乙铵。我们的研究结果表明，腺苷，通过腺苷酸环化酶和PKA途径，抑制的任务-1 K+通道。这导致去极化和激活Ca 2+通过VGCC进入。腺苷对I型细胞的这种兴奋作用可能有助于缺氧时颈动脉体的化学敏感性。
During hypoxia, the level of adenosine in the carotid bodies increases as a result of ATP catabolism and adenosine efflux via adenosine transporters. Using Ca2+ imaging, we found that adenosine, acting via A(2A) receptors, triggered a rise in cytoplasmic [Ca2+] ([Ca2+](i)) in type I (glomus) cells of rat carotid bodies. The adenosine response could be mimicked by forskolin (but not its inactive analog), and could be abolished by the PKA inhibitor H89. Simultaneous measurements of membrane potential (perforated patch recording) and [Ca2+](i) showed that the adenosine-mediated [Ca2+](i) rise was accompanied by depolarization. Ni2+, a voltage-gated Ca2+ channel (VGCC) blocker, abolished the adenosine-mediated [Ca2+](i) rise. Although adenosine was reported to inhibit a 4-aminopyridine (4-AP)-sensitive K+ current, 4-AP failed to trigger any [Ca2+](i) rise, or to attenuate the adenosine response. In contrast, anandamide, an inhibitor of the TWIK-related acid-sensitive K+-1 (TASK-1) channels, triggered depolarization and [Ca2+](i) rise. The adenosine response was attenuated by anandamide but not by tetraethylammonium. Our results suggest that adenosine, acting via the adenylate cyclase and PKA pathways, inhibits the TASK-1 K+ channels. This leads to depolarization and activation of Ca2+ entry via VGCC. This excitatory action of adenosine on type I cells may contribute to the chemosensitivity of the carotid body during hypoxia.