Sanguinetti M C, Spector P S
Department of Medicine, University of Utah, Salt Lake City 84112, USA.
Neuropharmacology. 1997 Jun;36(6):755-62. doi: 10.1016/s0028-3908(97)00029-4.
The molecular diversity of K(+)-selective channels far exceeds any other group of voltage- or ligand-gated channels, reflecting their early ancestral origin. This diversity is mirrored by the broad spectrum of physiological functions subserved by these proteins. Potassium channels modulate the resting potential and action potential duration of neurons, myocytes and endocrine cells and stabilize the membrane potential of excitable and nonexcitable cells. In addition to channel diversity, differential cellular expression of K+ channels determines the specific electrical responses to stimuli in a particular cell or tissue. This study reviews the recent genetic and physiological studies of congenital disorders caused by mutations in genes encoding K+ channels. These include the human disorders of episodic ataxia with myokymia, long QT syndrome and Bartter's syndrome, and weaver ataxia in mice. An understanding of the molecular basis of these diseases could facilitate the discovery and development of specific pharmacological therapies.
钾离子选择性通道的分子多样性远远超过任何其他电压门控或配体门控通道组,这反映了它们早期的祖先起源。这些蛋白质所发挥的广泛生理功能反映了这种多样性。钾离子通道调节神经元、心肌细胞和内分泌细胞的静息电位和动作电位持续时间,并稳定可兴奋细胞和不可兴奋细胞的膜电位。除了通道多样性外,钾离子通道在细胞中的差异表达决定了特定细胞或组织对刺激的特定电反应。本研究综述了最近关于由编码钾离子通道的基因突变引起的先天性疾病的遗传学和生理学研究。这些疾病包括伴有肌束震颤的发作性共济失调、长QT综合征和巴特综合征等人类疾病,以及小鼠的韦弗共济失调。了解这些疾病的分子基础有助于发现和开发特定的药物治疗方法。