We investigated changes in Na⁺currents (I_Na) in permanent (or chronic) atrial fibrillation (AF) and the effects of I_Nainhibition using ranolazine (Ran) on arrhythmias and contractility in human atrial myocardium.

Electrical remodeling during AF is typically associated with alterations in Ca²⁺and K⁺currents. It remains unclear whether I_Nais also altered.

Right atrial appendages from patients with AF (n = 23) and in sinus rhythm (SR) (n = 79) were studied.

Patch-clamp experiments in isolated atrial myocytes showed significantly reduced peak I_Nadensity (∼16%) in AF compared with SR, which was accompanied by a 26% lower expression of Nav1.5 (p < 0.05). In contrast, late I_Nawas significantly increased in myocytes from AF atria by ∼26%. Ran (10 μmol/l) decreased late I_Naby ∼60% (p < 0.05) in myocytes from patients with AF but only by ∼18% (p < 0.05) in myocytes from SR atria. Proarrhythmic activity was elicited in atrial trabeculae exposed to high [Ca²⁺]_oor isoprenaline, which was significantly reversed by Ran (by 83% and 100%, respectively). Increasing pacing rates from 0.5 to 3.0 Hz led to an increase in diastolic tension that could be significantly decreased by Ran in atria from SR and AF patients.

Na⁺channels may contribute to arrhythmias and contractile remodeling in AF. Inhibition of I_Nawith Ran had antiarrhythmic effects and improved diastolic function. Thus, inhibition of late I_Namay be a promising new treatment option for patients with atrial rhythm disturbances and diastolic dysfunction.