Background:
Atrial fibrillation (AF) is the most commonly reported cardiac arrhythmia. Current AF therapeutics lack efficacy, and mechanistic models to examine ion channel remodelling in AF are limited by a lack of atrial specificity in expression systems or low throughput methodologies. Much progress has recently been made in the development of automated patch-clamp (APC) systems that allow for high throughput electrophysiological measurements. APC could therefore be a useful tool for increasing the throughput of experiments involving complex AF-induced ionic remodelling events.
Methods:
We describe the application of a newly-designed high throughput APC device (Nanion Syncropatch 384) to investigate key currents and action potentials (AP) in human atrial-specific iPSC-derived cardiomyocytes (iPSC-CM), and in atrial cardiomyocytes directly isolated from native swine myocardium.
Results:
For the first time, we describe successful current and AP acquisition from native mammalian cardiomyocytes using APC (total: 203 atrial and 218 ventricular recordings from a single animal). We observed typical subtype-specific electrophysiological characteristics including a shorter AP and smaller L-type calcium current (ICa,L) in atrial preparations compared with ventricular in both iPSC-CM and native cardiomyocytes. In addition, Ba2+-sensitive inward rectifier potassium current (IK1) was smaller in atrial cells. Finally, activation of the atrial specific acetylcholine-activated inward rectifier potassium current (IK,ACh) was seen in atrial but not in ventricular cells following application of the M-receptor agonist carbachol (2 µM).
Conclusion:
The successful application of a high throughput APC-system for the recording of atrial APs and ionic currents in freshly isolated mammalian cardiomyocytes implies that APC constitutes a crucial tool for increasing the throughput of electrophysiological measurements of mammalian cardiac tissue. This will facilitate robust studies of AF mechanisms and substantially impact AF-related drug development programs.