Evolution of inwardly rectifying potassium channels and their gene expression in zebrafish embryos

Abstract

Background Inwardly rectifying potassium channels are essential for normal potassium homeostasis, maintaining the cellular resting membrane potential, and regulating electrolyte transportation. Mutations in Kir channels have been known to cause debilitating diseases ranging from neurological abnormalities to renal and cardiac failures. Many efforts have been made to understand their protein structures, physiological functions, and pharmacological modifiers. However, their expression and functions during embryonic development remain largely unknown. Results Using zebrafish as a model, we identified and renamed 31 kir genes. We also analyzed Kir gene evolution by phylogenetic and syntenic analyses. Our data indicated that the four subtypes of the Kir genes might have already evolved out in chordates. These vertebrate Kir genes most likely resulted from both whole‐genome duplications and tandem duplications. In addition, we examined zebrafish kir gene expression during early embryogenesis. Each subgroup's genes showed similar but distinct gene expression domains. The gene expression of ohnologous genes from teleost‐specific whole‐genome duplication indicated subfunctionalization. Varied temporal gene expression domains suggest that Kir channels may be needed for embryonic patterning or regulation. Conclusions Our phylogenetic and developmental analyses of Kir channels shed light on their evolutionary history and potential functions during embryogenesis related to congenital diseases and human channelopathies.

Evolution of two‐pore domain potassium channels and their gene expression in zebrafish embryos

“…However, many of the zebrafish k2p genes were temporally expressed at specific anatomic structures such as notochord ( kcnk6 ), somites ( kcnk4a ), pectoral fin ( kcnk4b , kcnk5b ), caudal fin fold ( kcnk4b ), and pancreas ( kcnk3b , kcnk9 ). This phenomenon is similar to zebrafish KCa and Kir channel genes, 48,55 suggesting that k2p genes are required not only for a specific physiological need but also for instructional signaling during developmental processes.…”

“…The six subtypes of K2P genes already existed in the invertebrates before the dawn of vertebrates (Figure 17A), similar to Kir channel genes. 48 After two rounds of WGDs (2Rs), all genes were doubled twice, which led to four copies of each gene. However, some of the ohnologs were lost immediately.…”

Zebrafish Embryos Display Characteristic Bioelectric Signals during Early Development

“…However, the underlying ion channels and connexins that generate these signals are unknown. Our recent gene expression analysis of calcium-gated potassium channels (KCa) and inwardly rectifying potassium channels (Kir) revealed that many ( kcnn1b , kcnn3 , kcnma1a , kcnma1b , kcnmb2b , kcnmb3 , kcnj4 , kcnj2a , kcnj2b , kcnj11 , kcnj5 , kcnj21 ) have a somite-specific expression at similar developmental stages [ 37 , 38 ]. Their presence in the developing somites may indicate that these channel activities underlie the tissue-level bioelectricity.…”

Bioelectricity in Developmental Patterning and Size Control: Evidence and Genetically Encoded Tools in the Zebrafish Model

“…For example, abundant ion regulators in different cell types within zebrafish somites and fins can be identified using this technique. Alternatively, whole mount in situ hybridization can be performed systematically, to examine their expression during zebrafish embryogenesis, as was performed in the case of the potassium channel gene subfamilies [ 281 , 282 ]. Once their gene expression is known, cell- and/or tissue-specific multiplexing gene knockout or knockdown by CRISPR can be used to examine certain ion regulators’ function in developmental patterning [ 283 , 284 , 285 , 286 , 287 ].…”