Lehmann-Horn F, Jurkat-Rott K
Department of Applied Physiology, University of Ulm, Ulm, Germany.
Physiol Rev. 1999 Oct;79(4):1317-72. doi: 10.1152/physrev.1999.79.4.1317.
By the introduction of technological advancement in methods of structural analysis, electronics, and recombinant DNA techniques, research in physiology has become molecular. Additionally, focus of interest has been moving away from classical physiology to become increasingly centered on mechanisms of disease. A wonderful example for this development, as evident by this review, is the field of ion channel research which would not be nearly as advanced had it not been for human diseases to clarify. It is for this reason that structure-function relationships and ion channel electrophysiology cannot be separated from the genetic and clinical description of ion channelopathies. Unique among reviews of this topic is that all known human hereditary diseases of voltage-gated ion channels are described covering various fields of medicine such as neurology (nocturnal frontal lobe epilepsy, benign neonatal convulsions, episodic ataxia, hemiplegic migraine, deafness, stationary night blindness), nephrology (X-linked recessive nephrolithiasis, Bartter), myology (hypokalemic and hyperkalemic periodic paralysis, myotonia congenita, paramyotonia, malignant hyperthermia), cardiology (LQT syndrome), and interesting parallels in mechanisms of disease emphasized. Likewise, all types of voltage-gated ion channels for cations (sodium, calcium, and potassium channels) and anions (chloride channels) are described together with all knowledge about pharmacology, structure, expression, isoforms, and encoding genes.
随着结构分析方法、电子学和重组DNA技术的技术进步，生理学研究已进入分子层面。此外，研究兴趣的焦点已从经典生理学转移，越来越集中在疾病机制上。正如本综述所表明的，这一发展的一个绝佳例子是离子通道研究领域，如果没有人类疾病来阐明，该领域几乎不可能取得如此进展。正是由于这个原因，离子通道的结构 - 功能关系和电生理学不能与离子通道病的遗传学和临床描述分开。在关于这个主题的综述中，独特之处在于描述了所有已知的电压门控离子通道的人类遗传性疾病，涵盖了医学的各个领域，如神经病学（夜间额叶癫痫、良性新生儿惊厥、发作性共济失调、偏瘫性偏头痛、耳聋、静止性夜盲）、肾脏病学（X连锁隐性肾结石、巴特综合征）、肌病学（低钾血症和高钾血症周期性麻痹、先天性肌强直、副肌强直、恶性高热）、心脏病学（长QT综合征），并强调了疾病机制中的有趣相似之处。同样，描述了所有类型的阳离子（钠、钙和钾通道）和阴离子（氯通道）电压门控离子通道，以及关于药理学、结构、表达、亚型和编码基因的所有知识。
