1. A microtranslatome coordinately regulates sodium and potassium currents in the human heart
- Author
-
Jennifer J. Knickelbine, Gail A. Robertson, Margaret B. Jameson, Erick B. Ríos-Pérez, Fang Liu, Catherine A. Eichel, and David K. Jones
- 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 - 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.
- Published
- 2019