Related Experiment Video
Updated: Aug 15, 2025

Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents
Published on: July 3, 2013
Differential Sodium Current Remodelling Identifies Distinct Cellular Proarrhythmic Mechanisms in Paroxysmal vs
Simona Casini1, Gerard A Marchal1, Makiri Kawasaki1
1Amsterdam UMC, location University of Amsterdam, Department of Experimental Cardiology, Amsterdam Cardiovascular Sciences, Heart failure & Arrhythmias, Amsterdam, The Netherlands.
Background:
The cellular mechanisms underlying progression from paroxysmal to persistent atrial fibrillation (AF) are not fully understood, but alterations in (late) sodium current (INa) have been proposed. Human studies investigating electrophysiological changes at the paroxysmal stage of AF are sparse, with the majority employing right atrial appendage cardiomyocytes (CMs). We here investigated action potential (AP) characteristics and (late) INa remodelling in left atrial appendage CMs (LAA-CMs) from patients with paroxysmal and persistent AF and patients in sinus rhythm (SR), as well as the potential contribution of the "neuronal" sodium channel SCN10A/NaV1.8.
Methods:
Peak INa, late INa and AP properties were investigated through patch-clamp analysis on single LAA-CMs, whereas quantitative polymerase chain reaction was used to assess SCN5A/SCN10A expression levels in LAA tissue.
Results:
In paroxysmal and persistent AF LAA-CMs, AP duration was shorter than in SR LAA-CMs. Compared with SR, peak INa and SCN5A expression were significantly decreased in paroxysmal AF, whereas they were restored to SR levels in persistent AF. Conversely, although late INa was unchanged in paroxysmal AF compared with SR, it was significantly increased in persistent AF. Peak or late Nav1.8-based INa was not detected in persistent AF LAA-CMs. Similarly, expression of SCN10A was not observed in LAAs at any stage.
Conclusions:
Our findings demonstrate differences in (late) INa remodeling in LAA-CMs from patients with paroxysmal vs persistent AF, indicating distinct cellular proarrhythmic mechanisms in different AF forms. These observations are of particular relevance when considering potential pharmacologic approaches targeting (late) INa in AF.
Related Concept Videos
Mechanism of Cardiac Arrhythmias
Electrophysiology of Normal Cardiac Rhythm
Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers
Class 1A Antiarrhythmic Drugs: These drugs work by moderately blocking sodium channels,...
ECG Interpretation of Arrhythmias II: Atrial, Junctional and Ventricular Arrhythmias
Dysrhythmias VI: Management of Dysrhythmias
Cardiac Action Potential
The cardiac action potential process involves a series of phases characterized by the movement of ions across the cardiac cell membranes, leading to the depolarization and repolarization of the cardiac myocytes.
Ionic Basis of Cardiac Action Potentials

