TREK-1 K+ channels couple angiotensin II receptors to membrane depolarization and aldosterone secretion in bovine adrenal glomerulosa cells
TREK-1 K+ channels couple angiotensin II receptors to membrane depolarization and aldosterone secretion in bovine adrenal glomerulosa cells
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DOI：
10.1152/ajpendo.00223.2004
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发表时间：
2004-12-01
影响因子：
5.1
通讯作者：
Enyeart, JJ
中科院分区：
文献类型：
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作者：
Enyeart, JA;Danthi, SJ;Enyeart, JJ
牛肾上腺肾小球（AZG）细胞显示表达bTREK-1背景K+通道，其设置静息膜电位并将血管紧张素II（ANG II）受体活化与膜去极化和醛固酮分泌偶联。北方印迹和原位杂交研究表明，bTREK-1 mRNA均匀分布在牛肾上腺皮质，包括束状核和球状核，但在髓质中不存在。在大鼠AZG细胞中编码主要背景K+通道的ASK-3 mRNA在牛肾上腺皮质中检测不到。在全细胞电压钳记录中，牛AZG细胞表达快速失活的电压门控K+电流和非失活背景K+电流，其性质共同将其鉴定为bTREK-1。通过细胞内酸化、ATP和bTREK-1开放剂（包括花生四烯酸（AA）和1- 3，4-二羟基-α-氰基肉桂酸肉桂酯（CDC））的灌流激活向外整流K+电流。牛嗜铬细胞不表达这种电流。在电压和电流钳记录中，ANG II（10 nM）选择性抑制非失活K+电流82.1 +/- 6.1%，去极化AZG细胞31.6 +/- 2.3 mV。CDC和AA压倒ANG II介导的bTREK-1抑制，并恢复静息膜电位，即使在持续存在的ANG II的控制值。加压素（50 nM），也在生理上刺激醛固酮分泌，抑制背景K+电流73.8 +/-9.4%。与其对bTREK-1的有效抑制相反，ANG II未能改变通过使用相同核苷酸和Ca 2+缓冲组合物的移液器溶液在宽范围的测试电位上测量的T型Ca 2+电流。ANG II也未能改变T通道激活的电压依赖性在这些相同的条件下。总体而言，这些结果将bTREK-1 K+通道确定为ANG II受体激活被转导为去极化依赖性Ca 2+进入和醛固酮分泌的关键控制点。
Bovine adrenal glomerulosa (AZG) cells were shown to express bTREK-1 background K+ channels that set the resting membrane potential and couple angiotensin II (ANG II) receptor activation to membrane depolarization and aldosterone secretion. Northern blot and in situ hybridization studies demonstrated that bTREK-1 mRNA is uniformly distributed in the bovine adrenal cortex, including zona fasciculata and zona glomerulosa, but is absent from the medulla. TASK-3 mRNA, which codes for the predominant background K+ channel in rat AZG cells, is undetectable in the bovine adrenal cortex. In whole cell voltage clamp recordings, bovine AZG cells express a rapidly inactivating voltage-gated K+ current and a noninactivating background K+ current with properties that collectively identify it as bTREK-1. The outwardly rectifying K+ current was activated by intracellular acidification, ATP, and superfusion of bTREK-1 openers, including arachidonic acid (AA) and cinnamyl 1-3,4-dihydroxy-alpha-cyanocinnamate (CDC). Bovine chromaffin cells did not express this current. In voltage and current clamp recordings, ANG II (10 nM) selectively inhibited the noninactivating K+ current by 82.1 +/- 6.1% and depolarized AZG cells by 31.6 +/- 2.3 mV. CDC and AA overwhelmed ANG II-mediated inhibition of bTREK-1 and restored the resting membrane potential to its control value even in the continued presence of ANG II. Vasopressin (50 nM), which also physiologically stimulates aldosterone secretion, inhibited the background K+ current by 73.8 +/- 9.4%. In contrast to its potent inhibition of bTREK-1, ANG II failed to alter the T-type Ca2+ current measured over a wide range of test potentials by using pipette solutions of identical nucleotide and Ca2+-buffering compositions. ANG II also failed to alter the voltage dependence of T channel activation under these same conditions. Overall, these results identify bTREK-1 K+ channels as a pivotal control point where ANG II receptor activation is transduced to depolarization-dependent Ca2+ entry and aldosterone secretion.