Channelopathies are a diverse group of human disorders that are caused by mutations in genes coding for ion channels or channel-regulating proteins. Several dozen channelopathies have been identified that involve both non-excitable cells as well as electrically active tissues like brain, skeletal and smooth muscle or the heart. In this review, we start out from the general question which ion channel genes are expressed tissue-selectively. We mined the human gene expression database Human Protein Atlas (HPA) for tissue-enriched ion channel genes and found 85 genes belonging to the ion channel families. Most of these genes were enriched in brain, testis and muscle and a complete list of the enriched ion channel genes is provided. We further focused on the tissue distribution of voltage-gated calcium channel (VGCC) genes including different brain areas and the retina based on the human gene expression from the FANTOM5 dataset. The expression data is complemented by an overview of the tissue-dependent aspects of L-type calcium channel (LTCC) function, dysfunction and pharmacology, as well as of their splice variants. Finally, we focus on the pathology of tissue-restricted LTCC channelopathies and their treatment options.
This article is part of the Special Issue entitled ‘Channelopathies.’