Analiza ewolucji kanalów potasowych KCNH u kręgowców i ich ekspresja u zarodków ryby zebry

Preprint (medRxiv/bioRxiv)➕ 25.05.2026Preprint (medRxiv/bioRxiv)

Evolutionary analysis of vertebrate KCNH voltage-gated potassium channels and their expression in zebrafish embryos

W skrócie

[Preprint - wstępne wyniki] Naukowcy zbadali ewolucję i ekspresję genów odpowiedzialnych za kanały potasowe KCNH u różnych kręgowców, identyfikując 14 takich genów u ryby zebry. Kanały te są ważne dla funkcjonowania mózgu i serca, a ich mutacje powodują epilepsję, zaburzenia rytmu serca i raka. Badania pokazały, że geny KCNH najpierw pojawiły się u bezkręgowców, a u kręgowców ich liczba wzrosła przez duplikacje całego genomu, przy czym większość była aktywna w tkankach nerwowych, a jeden gen (kcnh6a) wykazywał silną ekspresję w rozwijającym się sercu.

Oryginalny abstract (angielski)

Voltage-gated potassium channels (Kv) are a large family of potassium channels composed of 40 members across 12 subtypes. The KCNH genes encode 3 subfamilies of voltage-gated potassium channels: Kv10 (EAG, ether a go go), Kv11 (ERG, EAG-related gene), and Kv12 (ELK, EAG-like K). Kv channels play prominent roles in the neuronal and cardiovascular systems. Mutations in Kv channels have been linked to many human diseases, such as epilepsy, heart arrhythmias, and cancers. Significant progress has been made in understanding protein structures, physiological functions, and the pharmacological modifiers. However, the evolutionary history and gene expression of vertebrate KCNH genes during embryonic development remain largely unknown. We systematically identified and cloned 14 kcnh genes in zebrafish. Then, we examined vertebrate KCNH channel evolution by phylogenetic and syntenic analyses. Our data revealed that the three subtypes of the KCNH gene family have already evolved in invertebrates, long before the emergence of vertebrates. The number of vertebrate KCNH genes increased, most likely due to whole-genome duplications (WGDs). In addition, we examined zebrafish kcnh gene expression during early embryogenesis by in situ hybridization. Each subgroup's genes showed similar but distinct gene expression domains with some exceptions. Most of them were expressed in neural tissues. Notably, kcnh6a showed robust expression in the developing heart, consistent with its conserved role in cardiac repolarization. Additionally, a few kcnh genes were transiently expressed in nonneural tissues, such as somites and the notochord, suggesting they may have a unique role in embryonic development. Our phylogenetic and developmental analyses of KCNH channels shed light on their evolutionary history and potential roles during embryogenesis, in line with their physiological functions and human channelopathies.

Metadane publikacji

Journal
Preprint (medRxiv/bioRxiv)
Data publikacji
24.05.2026
DOI
10.64898/2026.05.21.726828
Europe PMC ID
PPR1237616
Autorzy
Wu K, Wang D, Dong Z, Zhou AY, Zhang G
Źródło
Preprint (medRxiv/bioRxiv)