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K~+通道在上皮细胞内以极化的方式表达,形成一个庞大的膜蛋白家族。出于对主要依赖Na~+-K~+-ATPase而维持的细胞内跨膜K~+梯度的考虑,K~+通道在跨上皮细胞转运中的主要作用为:膜电位生成和K~+循环。本文以肾近端小管和胃壁上皮细胞转运为例简要阐述了K~+通道的作用。在这两个组织中,K~+通道活性限速跨上皮细胞转运,调节细胞体积。近年来,药理学工具和转基因动物的实验证实了对K~+通道的原先认知,并将研究深入到分子水平。K~+通道的分子结构挑战高亲和力药物分子的设计,及其多组织同时表达的两个典型特征阻碍了高活性、组织特异性小分子治疗的进展。然而,抑制K~+通道能阻断胃酸分泌等病理生理机制的深入研究,促进K~+通道药物用于胃病治疗和作为肾脏转运抑制剂用于肾脏相关疾病治疗。
K ~ + channels are expressed in polarized manner in epithelial cells, forming a large family of membrane proteins. Due to the consideration of intracellular K ~ + gradient maintained by Na ~ + -K ~ + -ATPase, the main roles of K ~ + channels in trans-epithelial cell transport are: membrane potential generation and K ~ + cycle. In this paper, renal proximal tubule and gastric epithelial cell transport as an example to briefly explain the role of K ~ + channel. In both tissues, K ~ + channel activity translocates across epithelial cells and regulates cell volume. In recent years, experiments with pharmacological tools and transgenic animals have confirmed the original cognition of the K ~ + channel, and further studies have gone to the molecular level. Molecular Structure Challenges of K ~ + Channels Two typical features of the design of high-affinity drug molecules and their simultaneous multi-tissue organization have hindered the progress of high-activity, tissue-specific small molecule therapy. However, the inhibition of K ~ + channel can block the gastric acid secretion and other pathophysiological mechanisms in-depth study, and promote K ~ + channel drugs for the treatment of stomach and renal transport inhibitors for the treatment of kidney disease.