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 <i>I</i>_Na and <i>I</i>_Kr channels (<i>SCN5A</i> and <i>hERG</i>, respectively) are associated in defined complexes during protein translation. Using biochemical, electrophysiological and single-molecule fluorescence localization approaches, we find that roughly half the <i>hERG</i> translational complexes contain <i>SCN5A</i> 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.