PUBLICATION

Kcnh1 voltage-gated potassium channels are essential for early zebrafish development

Authors
Stengel, R., Rivera-Milla, E., Sahoo, N., Ebert, C., Bollig, F., Heinemann, S.H., Schonherr, R., and Englert, C.
ID
ZDB-PUB-120830-39
Date
2012
Source
The Journal of biological chemistry   287(42): 35565-35575 (Journal)
Registered Authors
Bollig, Frank, Englert, Christoph, Rivera-Milla, Eric
Keywords
development, electrophysiology, neurodevelopment, potassium channels, zebrafish, EAG1 channel, morpholino
MeSH Terms
  • Animals
  • Body Patterning/physiology*
  • Cyclin D1/genetics
  • Cyclin D1/metabolism
  • Cyclin-Dependent Kinase Inhibitor Proteins/genetics
  • Cyclin-Dependent Kinase Inhibitor Proteins/metabolism
  • Female
  • Gene Expression Regulation, Developmental/physiology*
  • Humans
  • Male
  • Organ Specificity/physiology
  • Potassium Channels, Voltage-Gated/biosynthesis*
  • Potassium Channels, Voltage-Gated/genetics
  • Rhombencephalon/embryology
  • Transcription, Genetic/physiology*
  • Xenopus laevis
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/biosynthesis*
  • Zebrafish Proteins/genetics
PubMed
22927438 Full text @ J. Biol. Chem.
Abstract

The Kcnh1 gene encodes a voltage-gated potassium channel highly expressed in neurons and involved in tumor cell proliferation, yet its physiological roles remain unclear. We have used the zebrafish as a model to analyze Kcnh1 function in vitro and in vivo. We found that the kcnh1 gene is duplicated in teleost fish (i.e., kcnh1a and kcnh1b) and that both genes are maternally expressed during early development. In adult zebrafish, kcnh1a and kcnh1b have distinct expression patterns, but share expression in brain and testis. Heterologous expression of both genes in Xenopus oocytes revealed a strong conservation of characteristic functional properties between human and fish channels, including a unique sensitivity to intracellular Ca2+/calmodulin and modulation of voltage-dependent gating by extracellular Mg2+. Using a morpholino antisense approach, we demonstrate a strong kcnh1 loss-of-function phenotype in developing zebrafish, characterized by growth retardation, delayed hindbrain formation, and embryonic lethality. This late phenotype was preceded by transcriptional upregulation of known cell-cycle inhibitors (p21, p27, cdh2) and downregulation of pro-proliferative factors, including cyclin D1, at 70% epiboly. These results reveal an unanticipated basic activity of kcnh1, which is crucial for early embryonic development and patterning.

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