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Coordinating heart morphogenesis: A novel role for hyperpolarization-activated cyclic nucleotide-gated (HCN) channels

Emily Pitcairn1, Hannah Harris1, Justine Epiney1

  • 1Department of Biology and Allen Discovery Center at Tufts University, Medford, MA, USA.

Communicative & Integrative Biology
|July 14, 2017
PubMed

Insights

Hyperpolarization-activated cyclic-nucleotide gated channel 4 (HCN4) is crucial for embryonic heart development. Altering HCN4 function in Xenopus embryos disrupts heart formation and gene expression, revealing its role in early cardiac morphogenesis.

Area of Science:

  • Developmental Biology
  • Cardiovascular Physiology
  • Molecular Genetics

Background:

  • Hyperpolarization-activated cyclic-nucleotide gated (HCN) channels regulate neuronal and cardiac excitability.
  • HCN4 is identified as the primary pacemaker channel in adult vertebrate hearts.
  • The role of HCN4 during embryonic development remains largely uncharacterized.

Purpose of the Study:

  • To characterize the embryonic expression profile of HCN4 in *Xenopus laevis*.
  • To investigate the functional consequences of altering HCN4 activity during early embryogenesis.
  • To elucidate the role of HCN4 in embryonic heart morphogenesis and pattern formation.

Main Methods:

  • Expression profiling of HCN4 during *Xenopus laevis* development.
  • Overexpression and dominant-negative mRNA injection of HCN4 in *Xenopus* embryos.
  • Analysis of key patterning gene expression and cardiac morphology.

Main Results:

  • HCN4 exhibits a distinct expression pattern during *Xenopus* embryogenesis.
  • Both HCN4 overexpression and dominant-negative inhibition lead to severe cardiac malformations.
  • Altered HCN4 function results in improper expression of critical developmental patterning genes.

Conclusions:

  • HCN4 plays a vital role in coordinating cardiac morphogenesis during *Xenopus* embryogenesis.
  • HCN4 influences the expression of genes that provide positional information for heart development.
  • This study establishes HCN4 as a key regulator of early heart development.

Keywords:
HCN4bioelectricitycardiogenesision channelmembrane potentialmorphogenesispositional identity

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