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September 12, 2009Journal of Biological ChemistryOpen Access

Rescue of a Trafficking Defective Human Pacemaker Channel via a Novel Mechanism

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Why the study?

Does enhanced tyrosine phosphorylation by Src kinases rescue the trafficking and current expression of the HCN4 D553N mutant channel?

Population

In vitro model expressing the hyperpolarization-activated cyclic nucleotide-gated HCN4 pacemaker channel…

Comparison

Enhanced tyrosine phosphorylation mediated by… vs Unrescued D553N mutant channel

Design

Preclinical

Authors

YLYen‐Chang LinChinese Culture UniversityJHJianying HuangYale UniversityHKHong KanEli Lilly (United States)

Discussion

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Implication

Src-mediated tyrosine phosphorylation may restore HCN4 D553N function; leaves open translation to human long QT therapies.

Structured PICO

Does enhanced tyrosine phosphorylation by Src kinases rescue the trafficking and current expression of the HCN4 D553N mutant channel?

P
Population
In vitro model expressing the hyperpolarization-activated cyclic nucleotide-gated HCN4 pacemaker channel mutant (D553N) associated with cardiac arrhythmias including long QT
I
Intervention
Enhanced tyrosine phosphorylation mediated by Src, Fyn, and Yes kinases
C
Comparator
Unrescued D553N mutant channel
O
Outcome
Surface expression and ionic current expression of the D553N mutant channelsurrogate

Enhanced tyrosine phosphorylation by endogenous Src kinases represents a novel mechanism to rescue the trafficking and function of the long QT-associated HCN4 D553N mutant channel.

Cite This Study

Lin et al. (2009) studied this question.

synapsesocial.com/papers/6a928de36cd82e562097a166https://doi.org/10.1074/jbc.m109.039180
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Functional Characterization of a Trafficking-defective HCN4 Mutation, D553N, Associated with Cardiac Arrhythmia2004 · 229 citations
  2. 2A Novel Mutation (T65P) in the PAS Domain of the Human Potassium Channel HERG Results in the Long QT Syndrome by Trafficking Deficiency2002 · 95 citations
  3. 3Novel Mechanism Associated With an Inherited Cardiac Arrhythmia1999 · 193 citations
  4. 4Thapsigargin Selectively Rescues the Trafficking Defective LQT2 Channels G601S and F805C2003 · 98 citations
  5. 5HCN Pacemaker Channel Activation Is Controlled by Acidic Lipids Downstream of Diacylglycerol Kinase and Phospholipase A22007 · 56 citations