A195V mutation identified in sudden cardiac death decreases membrane localization and activation current density and abolishes cAMP sensitivity of HCN4 channels Article Swipe
Qiuping Wu
,
Kai Zhang
,
Jiacheng Yue
,
Bingjie Hu
,
Jianding Cheng
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-2466162/v1
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-2466162/v1
Mutation A195V in hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) channel was identified to be genetically associated with sudden unexplained nocturnal death syndrome (SUNDS) and sudden infant death syndrome (SIDS) by us and other group, respectively. However, the underlying mechanism by which this rare variant causes SUNDS and SIDS remains unknow. In this study, HEK293 cells were transfected with wild type or mutant A195V HCN4 plasmid. qPCR, western blot and confocal analysis were conducted to analyze the expression of HCN4 channels. Whole cell clamp was used to analyze the activation current and tail current of HCN4 channels with and without cAMP stimulation. The results showed that A195V decreased the expression and membrane localization of HCN4 channels. Consistent with this, A195V also decreased the activation current density of HCN4 channels under − 140mV to -100mv and under − 50mV to -40mV. The present study was the first to clarify the decreased expression of HCN4 protein and the decreased activation current density and abolished cAMP sensitivity of HCN4 channels caused by A195V, which biophysically confirmed HCN4 A195V as the pathogenic variation for SUNDS and SIDS.
Related Topics
Concepts
Sudden infant death syndrome
Sudden death
Patch clamp
HCN channel
HEK 293 cells
Western blot
Mutant
Transfection
Membrane potential
Electrophysiology
Biology
Mutation
Stimulation
Ion channel
Cell biology
Molecular biology
Internal medicine
Genetics
Gene
Endocrinology
Medicine
Biophysics
Neuroscience
Pediatrics
Receptor
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.21203/rs.3.rs-2466162/v1
- https://www.researchsquare.com/article/rs-2466162/latest.pdf
- OA Status
- green
- Cited By
- 1
- References
- 35
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4327582630
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4327582630Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.21203/rs.3.rs-2466162/v1Digital Object Identifier
- Title
-
A195V mutation identified in sudden cardiac death decreases membrane localization and activation current density and abolishes cAMP sensitivity of HCN4 channelsWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-03-16Full publication date if available
- Authors
-
Qiuping Wu, Kai Zhang, Jiacheng Yue, Bingjie Hu, Jianding ChengList of authors in order
- Landing page
-
https://doi.org/10.21203/rs.3.rs-2466162/v1Publisher landing page
- PDF URL
-
https://www.researchsquare.com/article/rs-2466162/latest.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.researchsquare.com/article/rs-2466162/latest.pdfDirect OA link when available
- Concepts
-
Sudden infant death syndrome, Sudden death, Patch clamp, HCN channel, HEK 293 cells, Western blot, Mutant, Transfection, Membrane potential, Electrophysiology, Biology, Mutation, Stimulation, Ion channel, Cell biology, Molecular biology, Internal medicine, Genetics, Gene, Endocrinology, Medicine, Biophysics, Neuroscience, Pediatrics, ReceptorTop concepts (fields/topics) attached by OpenAlex
- Cited by
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1Total citation count in OpenAlex
- Citations by year (recent)
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2025: 1Per-year citation counts (last 5 years)
- References (count)
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35Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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