Angiotensin II stimulates T-type Ca2+ channel currents via activation of a G protein, G(i)
Angiotensin II stimulates T-type Ca2+ channel currents via activation of a G protein, G(i)
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DOI：
10.1152/ajpcell.1996.271.4.c1340
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发表时间：
1996-10-01
影响因子：
5.5
通讯作者：
Barrett, PQ
中科院分区：
文献类型：
--
作者：
Lu, HK;Fern, RJ;Barrett, PQ
血管紧张素II（Angiotensin II，ANG II）是肾上腺肾小球合成和分泌醛固酮的最有效和最重要的生理刺激剂。由于肾上腺肾小球（AG）细胞的类固醇生成部分由通过T型和L型Ca 2+通道的Ca 2+内流介导，因此我们评估了T型Ca 2+通道是否受ANG II调节。我们观察到ANG II通过将通道激活的电压依赖性转移到更负的电位来增强T型Ca 2+电流。这种转变由ANG II 1型受体转导。激素的作用不受Ca 2 +/钙调蛋白依赖性蛋白激酶II（CaMKII）介导，因为它不受CaMKII（（281-302））（激酶催化区的肽抑制剂）的阻止。相反，这种转变是由G蛋白G（i）的活化介导的，因为用百日咳毒素进行细胞预处理和用针对重组G（i）α产生的单克隆抗体进行细胞透析可以消除G（i）。ANG II对T型Ca 2+通道的这种作用应在生理相关电压下增加AG细胞中的Ca 2+内流，并导致醛固酮分泌的持续增加。
Angiotensin II (ANG II) is the most potent and the most physiologically important stimulator of aldosterone synthesis and secretion from the adrenal zona glomerulosa. Because steroidogenesis by adrenal glomerulosa (AG) cells is mediated in part by Ca2+ influx through T- and L-type Ca2+ channels, we evaluated whether T-type Ca2+ channels are regulated by ANG II. We observe that ANG II enhances T-type Ca2+ current by shifting the voltage dependence of channel activation to more negative potentials. This shift is transduced by the ANG II type 1 receptor. The effect of the hormone is not mediated by Ca2+/calmodulin-dependent protein kinase II (CaMKII) as it is not prevented by CaMKII((281-302)), a peptide inhibitor of the catalytic region of the kinase. Rather, this shift is mediated by the activation of a G protein, G(i), because it is abolished by cell pretreatment with pertussis toxin and by cell dialysis with a monoclonal antibody generated against recombinant G(i) alpha. This effect of ANG II on T-type Ca2+ channels should increase Ca2+ entry in AG cells at physiologically relevant voltages and result in a sustained increase in aldosterone secretion.