What question did this study set out to answer?

Investigate how developmentally regulated alternative splice variants of the auxiliary protein TRIP8b regulate the subcellular trafficking, localization, and biophysical properties of HCN1 channels.

May 13, 2009Journal of NeuroscienceOpen Access

Alternatively Spliced Isoforms of TRIP8b Differentially Control h Channel Trafficking and Function

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Authors

ALAlan S. LewisAlbany Medical Center Hospital ESEmily SchwartzBoston College CCC. Savio ChanChinese University of Hong Kong

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Implication

Laboratory investigation demonstrates alternative TRIP8b isoforms differentially modulate HCN1 channel trafficking and current in hippocampal neurons, highlighting targets for epilepsy.

Key Points

Investigate how developmentally regulated alternative splice variants of the auxiliary protein TRIP8b regulate the subcellular trafficking, localization, and biophysical properties of HCN1 channels.
Co-expressed distinct TRIP8b splice variants with HCN1 channels in heterologous cell systems and cultured hippocampal neurons to evaluate gating, current density, and surface expression.
Assessed isoform-specific subcellular localization of HCN1 in hippocampal dendrites.
Performed shRNA-mediated knockdown of endogenous TRIP8b in hippocampal neurons to determine its impact on native I(h) currents.
All TRIP8b splice variants bound HCN1 via dual C-terminal interaction sites and caused a hyperpolarizing shift in channel voltage dependence, but exerted opposing effects by either upregulating or downregulating I(h) current density and surface expression.
Coexpression in hippocampal neurons revealed that TRIP8b isoforms induce isoform-specific alterations in HCN1 subcellular localization.
Knockdown of TRIP8b with shRNA significantly reduced native I(h) in hippocampal neurons, demonstrating that the predominant isoforms in the brain function to enhance channel surface expression.

Cite This Study

Lewis et al. (2009) studied this question.

synapsesocial.com/papers/6a71722784cc45bb7bdff292 https://doi.org/10.1523/jneurosci.0856-09.2009

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Implication

Laboratory investigation demonstrates alternative TRIP8b isoforms differentially modulate HCN1 channel trafficking and current in hippocampal neurons, highlighting targets for epilepsy.

Alternatively Spliced Isoforms of TRIP8b Differentially Control h Channel Trafficking and Function

Discussion

Member takes

Implication

Key Points

Cite This Study

Alternatively Spliced Isoforms of TRIP8b Differentially Control h Channel Trafficking and Function

Discussion

Member takes

Implication

Key Points

Cite This Study

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