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.

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It is widely accepted that aldosterone induces atrial fibrillation (AF) by promoting structural changes, but its effects on the function of primary atrial myocytes remain unknown. We have investigated this point in adult rat atrial myocytes, chronically exposed to the hormone. This treatment produced larger amplitude of Ca transients, longer action potential (AP) duration, and higher incidence of unsynchronized Ca oscillations. Moreover, it also gave rise to increases in both cell membrane capacitance (C, 30 %) and activity of L-type Ca channels (LTCCs, 100 %). Concerning K currents, a twofold increase was also observed, but only in a delayed rectifier component (I). Interestingly, the maximal conductance (G) of Na channels was also enhanced, but it occurred in the face of a negative shift in the voltage dependence of inactivation. Thus, at physiological potentials, a decreased fraction of available channels neutralized the effect on G. With regard to the effects on both C and LTCCs, they involved activation of mineralocorticoid receptors (MRs), were dose-dependent (EC ∼20-130 nM), and developed and recovered in days. Neither gating currents nor protein levels of LTCCs were altered. Instead, the effect on LTCCs was mimicked by cAMP, reverted by a PKA inhibitor, and attenuated by a nitric oxide donor (short-term exposures). Both EGTA and the antioxidant NAC prevented the increase in C, without significantly interfering with the upregulation of LTCCs. Overall, these results show that chronic exposures to aldosterone result in dire functional changes at the single myocyte level, which may explain the link between aldosteronism and AF.