Lu H K, Fern R J, Luthin D, Linden J, Liu L P, Cohen C J, Barrett P Q
Department of Pharmacology, University of Virginia, Charlottesville 22908, USA.
Am J Physiol. 1996 Oct;271(4 Pt 1):C1340-9. doi: 10.1152/ajpcell.1996.271.4.C1340.
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, Gi, because it is abolished by cell pretreatment with pertussis toxin and by cell dialysis with a monoclonal antibody generated against recombinant Gi 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.
血管紧张素II（ANG II）是肾上腺球状带醛固酮合成与分泌最有效且在生理上最重要的刺激物。由于肾上腺球状带（AG）细胞的类固醇生成部分是由通过T型和L型钙通道的Ca2+内流介导的，我们评估了T型钙通道是否受ANG II调节。我们观察到ANG II通过将通道激活的电压依赖性向更负的电位移动来增强T型钙电流。这种移动是由ANG II 1型受体转导的。该激素的作用不是由Ca2+/钙调蛋白依赖性蛋白激酶II（CaMKII）介导的，因为它不会被激酶催化区域的肽抑制剂CaMKII(281 - 302)所阻止。相反，这种移动是由G蛋白Gi的激活介导的，因为用百日咳毒素对细胞进行预处理以及用针对重组Giα产生的单克隆抗体对细胞进行透析可消除这种移动。ANG II对T型钙通道的这种作用应会在生理相关电压下增加AG细胞中的Ca2+内流，并导致醛固酮分泌持续增加。
