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A microtranslatome coordinately regulates sodium and potassium currents in the human heart.

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.

SUBMITTER: Eichel CA

PROVIDER: S-EPMC6867827 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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A microtranslatome coordinately regulates sodium and potassium currents in the human heart.

Eichel Catherine A CA Ríos-Pérez Erick B EB Liu Fang F Jameson Margaret B MB Jones David K DK Knickelbine Jennifer J JJ Robertson Gail A GA

eLife 20191031

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 fluoresc ...[more]

PMID: 31670657

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