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Commun Integr Biol 2017 May 10;103:e1309488. doi: 10.1080/19420889.2017.1309488.
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Coordinating heart morphogenesis: A novel role for hyperpolarization-activated cyclic nucleotide-gated (HCN) channels during cardiogenesis in Xenopus laevis.

Pitcairn E , Harris H , Epiney J , Pai VP , Lemire JM , Ye B , Shi NQ , Levin M , McLaughlin KA .

Hyperpolarization-activated cyclic-nucleotide gated channel (HCN) proteins are important regulators of both neuronal and cardiac excitability. Among the 4 HCN isoforms, HCN4 is known as a pacemaker channel, because it helps control the periodicity of contractions in vertebrate hearts. Although the physiological role of HCN4 channel has been studied in adult mammalian hearts, an earlier role during embryogenesis has not been clearly established. Here, we probe the embryonic roles of HCN4 channels, providing the first characterization of the expression profile of any of the HCN isoforms during Xenopus laevis development and investigate the consequences of altering HCN4 function on embryonic pattern formation. We demonstrate that both overexpression of HCN4 and injection of dominant-negative HCN4 mRNA during early embryogenesis results in improper expression of key patterning genes and severely malformed hearts. Our results suggest that HCN4 serves to coordinate morphogenetic control factors that provide positional information during heart morphogenesis in Xenopus.

PubMed ID: 28702127
PMC ID: PMC5501196
Article link: Commun Integr Biol

Species referenced: Xenopus laevis
Genes referenced: bmp4 hcn2 hcn4 lefty nkx2-5 nodal nodal1 otx2 pitx2 shh tbx18 tbxt tnnt2
Antibodies: Tnnt2 Ab1

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References [+] :
Accili, From funny current to HCN channels: 20 years of excitation. 2002, Pubmed