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A microtranslatome coordinately regulates sodium and potassium currents in the human heart
- Source :
- eLife, Vol 8 (2019), eLife
- Publication Year :
- 2019
- Publisher :
- eLife Sciences Publications Ltd, 2019.
-
Abstract
- Catastrophic arrhythmias and sudden cardiac death can occur with even a small imbalance between inward sodium currents and outward potassium currents, but mechanisms establishing this critical balance are not understood. Here, we show that mRNA transcripts encoding INa and IKr channels (SCN5A and hERG, respectively) are associated in defined complexes during protein translation. Using biochemical, electrophysiological and single-molecule fluorescence localization approaches, we find that roughly half the hERG translational complexes contain SCN5A transcripts. Moreover, the transcripts are regulated in a way that alters functional expression of both channels at the membrane. Association and coordinate regulation of transcripts in discrete ‘microtranslatomes’ represents a new paradigm controlling electrical activity in heart and other excitable tissues.
- Subjects :
- 0301 basic medicine
ERG1 Potassium Channel
Structural Biology and Molecular Biophysics
Potassium
030204 cardiovascular system & hematology
NAV1.5 Voltage-Gated Sodium Channel
0302 clinical medicine
action potential
KCNH2
Biology (General)
SCN5A
biology
General Neuroscience
cotranslation
ion channels
Heart
General Medicine
Cell biology
Medicine
Research Article
Human
congenital, hereditary, and neonatal diseases and abnormalities
QH301-705.5
Sodium
Science
hERG
chemistry.chemical_element
Transfection
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
co-knockdown
Humans
RNA, Messenger
cardiovascular diseases
Ion channel
Messenger RNA
General Immunology and Microbiology
Human heart
Cell Biology
Electrophysiology
HEK293 Cells
030104 developmental biology
Gene Expression Regulation
chemistry
Structural biology
Protein Biosynthesis
biology.protein
Subjects
Details
- Language :
- English
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- eLife
- Accession number :
- edsair.doi.dedup.....9dfe4d233cc1062643c5048b9b72dc0f