Jegla Timothy J, Zmasek Christian M, Batalov Serge, Nayak Surendra K
The Scripps Research Institute, La Jolla, CA 92037, USA.
Comb Chem High Throughput Screen. 2009 Jan;12(1):2-23. doi: 10.2174/138620709787047957.
Ion channels are intimately involved in virtually every physiological process of consequence in humans. Their importance is underscored by the identification of numerous "channelopathies", human diseases caused by ion channel mutations. Ion Channels have consequently been viewed as fertile ground for drug discovery and, indeed, they represent one of the largest target classes for current medicines. The future prospects of ion channels as a target class are tied to the functional characterization of the human ion channel set on a genomic scale. The focus of this review is to describe the molecular diversity and conservation of human ion channels. The human genome contains at least 232 genes that encode the pore-forming subunits of plasma membrane ion channels. Comparative genome analysis shows that most human ion channel gene families have their origins in the earliest metazoans but the human genes are largely derived from duplications that took place in the vertebrate lineage. The mouse and human ion channel gene sets are virtually identical, but differ significantly from fish channel sets. Genome comparisons highlight a number of highly conserved channel families that do not yet have specifically defined functional roles in vivo. These channel families are likely to have non-redundant functions in metazoans and represent some of the best new opportunities for channel target prospecting. Furthermore, genome-wide patterns of sequence conservation can now be used to refine strategies for the identification of gene-specific channel probes.
离子通道几乎参与了人类所有重要的生理过程。众多“离子通道病”（由离子通道突变引起的人类疾病）的发现凸显了它们的重要性。因此，离子通道被视为药物研发的沃土，实际上，它们是当前药物最大的靶点类别之一。离子通道作为一个靶点类别的未来前景与在基因组规模上对人类离子通道组的功能表征紧密相关。本综述的重点是描述人类离子通道的分子多样性和保守性。人类基因组至少包含232个编码质膜离子通道孔形成亚基的基因。比较基因组分析表明，大多数人类离子通道基因家族起源于最早的后生动物，但人类基因大多源自脊椎动物谱系中发生的基因复制。小鼠和人类的离子通道基因集几乎相同，但与鱼类的通道集有显著差异。基因组比较突出了一些高度保守的通道家族，它们在体内尚未有明确界定的功能作用。这些通道家族可能在后生动物中具有非冗余功能，是通道靶点探索的一些最佳新机会。此外，全基因组序列保守模式现在可用于完善鉴定基因特异性通道探针的策略。
