McCoy D E, Guggino S E, Stanton B A
Department of Physiology, Dartmouth Medical School, Hanover, New Hampshire, USA.
Kidney Int. 1995 Oct;48(4):1125-33. doi: 10.1038/ki.1995.396.
Cyclic nucleotide-gated cation channels, which are permeable to monovalent and divalent cations, are expressed in a number of tissues. cDNAs encoding cGMP-gated cation channel subunits have been cloned in retinal rods, cones, olfactory neuroepithelium, pineal gland, aorta, testis, heart, and most recently kidney. Patch clamp studies have identified and characterized cGMP-gated cation channels in the cortical collecting duct (CCD) and inner medullary collecting duct (IMCD). cGMP-gated cation channels in kidney share many biophysical and molecular properties with the retinal rod cGMP-gated channel. However, unlike the retinal rod channel, the cGMP-gated cation channel in kidney is inhibited by cGMP and stimulated by increased calcium levels. In the IMCD the cGMP-gated cation channel mediates electrogenic sodium absorption which is inhibited by ANP via cGMP. Recently, cGMP-gated cation channel poly(A+) RNA has been identified in other nephron segments by RT-PCR and in situ PCR hybridization. Furthermore, cGMP-gated cation channel protein has also been identified in all nephron segments by Western blot analysis. These observations suggest that cGMP-gated cation channels, or closely related gene products, may play an important physiological role in all nephron segments. Hormones that increase intracellular cGMP may regulate sodium, and perhaps calcium, uptake in nephron segments proximal to the IMCD. Increases in cell sodium and calcium may regulate other transport and signaling pathways.
环核苷酸门控阳离子通道对单价和二价阳离子具有通透性，在多种组织中均有表达。编码cGMP门控阳离子通道亚基的cDNA已在视网膜视杆细胞、视锥细胞、嗅神经上皮、松果体、主动脉、睾丸、心脏以及最近发现的肾脏中克隆出来。膜片钳研究已在皮质集合管（CCD）和髓质内集合管（IMCD）中鉴定并表征了cGMP门控阳离子通道。肾脏中的cGMP门控阳离子通道与视网膜视杆细胞cGMP门控通道具有许多生物物理和分子特性。然而，与视网膜视杆细胞通道不同的是，肾脏中的cGMP门控阳离子通道受cGMP抑制，并受钙水平升高的刺激。在IMCD中，cGMP门控阳离子通道介导电中性钠吸收，心房钠尿肽通过cGMP对其产生抑制作用。最近，通过逆转录聚合酶链反应（RT-PCR）和原位PCR杂交，在其他肾单位节段中鉴定出了cGMP门控阳离子通道多聚腺苷酸（poly(A+)）RNA。此外，通过蛋白质免疫印迹分析，在所有肾单位节段中也鉴定出了cGMP门控阳离子通道蛋白。这些观察结果表明，cGMP门控阳离子通道或密切相关的基因产物可能在所有肾单位节段中发挥重要的生理作用。增加细胞内cGMP的激素可能调节IMCD近端肾单位节段中的钠摄取，或许还能调节钙摄取。细胞内钠和钙的增加可能调节其他转运和信号通路。
