Channels and Disease

Connexin 43 (Cx43) is a gap junction protein expressed in various tissues and organs of vertebrates. Besides functioning as a gap junction, Cx43 also regulates diverse cellular processes like cell growth and differentiation, cell migration, cell survival, etc. Cx43 is critical for normal cardiac functioning and is therefore abundantly expressed in cardiomyocytes. On the other hand, ATP-sensitive potassium (K) channels are metabolic sensors converting metabolic changes into electrical activity. These channels are important in maintaining the neurotransmitter release, smooth muscle relaxation, cardiac action potential repolarization, normal physiology of cellular repolarization, insulin secretion and immune function. Cx43 and K channels are part of the same signaling pathway, regulating cell survival during stress conditions and ischemia/hypoxia preconditioning. However, the underlying molecular mechanism for their combined role in ischemia/hypoxia preconditioning is largely unknown. The current review focuses on understanding the molecular mechanism responsible for the coordinated role of Cx43 and K channel protein in protecting cardiomyocytes against ischemia/hypoxia stress.

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Bioinformatic analysis of human CNS-expressed ion channels as candidates for episodic nervous system disorders

Freudenberg

Ptáček

2007

Neurogenetics

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As monogenic forms of episodic nervous system disorders are often caused by ion channel mutations, we looked for features of human central nervous system (CNS) expressed ion channels that further our understanding of those phenotypes. To this end, we compared human ion channels with other CNS-expressed genes, which we categorized according to the existence of transmembrane domains. When looking at the phylogenetic distribution of these genes, we observed an increased percentage of ion channels that exist in vertebrate genomes while missing in invertebrate genomes. Because we hypothesized that this pattern may relate to a more specific expression, we searched for characteristics of ion channels that indicate a tighter expression regulation. We found that ion channels have longer intron and protein sequences, features typical of genes with more specific expression. In addition, ion channels have increased human-rodent conservation around their transcription start site, as indicated by a higher fraction of conserved noncoding regions. This points to a high relevance of mutations that regulate ion channel expression. When we finally asked whether vertebrate-specific diversification is also displayed by non-ion channel genes with important roles in the CNS, we found a similar phylogenetic distribution. This concordant phylogenetic pattern suggests that vertebrate-specific adaptations may account for a large part of the shared genetic basis of episodic CNS disorders, including monogenic and genetically complex disease manifestations. Consequently, this phylogenetic pattern may contribute to the prioritization of candidate genes in human genetic studies of episodic CNS disorders.

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Channels and Disease

Cited by 13 publications

References 11 publications

Calcium-Activated K+ Channels (KCa) and Therapeutic Implications

Calcium-Activated K+ Channels (KCa) and Therapeutic Implications

Connexin 43 and ATP-sensitive potassium channels crosstalk: a missing link in hypoxia/ischemia stress

Bioinformatic analysis of human CNS-expressed ion channels as candidates for episodic nervous system disorders

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