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Late sodium current in synergism with Ca2+/calmodulin-dependent protein kinase II contributes to β-adrenergic activation-induced atrial fibrillation.
- Source :
- Philosophical Transactions of the Royal Society B: Biological Sciences; 6/19/2023, Vol. 378 Issue 1879, p1-9, 9p
- Publication Year :
- 2023
-
Abstract
- Atrial fibrillation (AF) is frequently associated with β-adrenergic stimulation, especially in patients with structural heart diseases. The objective of this study was to determine the synergism of late sodium current (late I<subscript>Na</subscript>) and Ca<superscript>2+</superscript>/calmodulin-dependent protein kinase (CaMKII)-mediated arrhythmogenic activities in β-adrenergic overactivation-associated AF. Monophasic action potential, conduction properties, protein phosphorylation, ion currents and cellular trigger activities were measured from rabbit-isolated hearts, atrial tissue and atrial myocytes, respectively. Isoproterenol (ISO, 1–15 nM) increased atrial conduction inhomogeneity index, phospho-Na<subscript>v</subscript>1.5 and phospho-CaMKII protein levels and late I<subscript>Na</subscript> by 108%, 65%, 135% and 87%, respectively, and induced triggered activities and episodes of AF in all hearts studied (p < 0.05). Sea anemone toxin II (ATX-II, 2 nM) was insufficient to induce any atrial arrhythmias, whereas the propensities of AF were greater in hearts treated with a combination of ATX-II and ISO. Ranolazine, eleclazine and KN-93 abolished ISO-induced AF, attenuated the phosphorylation of Na<subscript>v</subscript>1.5 and CaMKII, and reversed the increase of late I<subscript>Na</subscript> (p < 0.05) in a synergistic mode. Overall, late I<subscript>Na</subscript> in association with the activation of CaMKII potentiates β-adrenergic stimulation-induced AF and the inhibition of both late I<subscript>Na</subscript> and CaMKII exerted synergistic anti-arrhythmic effects to suppress atrial arrhythmic activities associated with catecholaminergic activation. This article is part of the theme issue 'The heartbeat: its molecular basis and physiological mechanisms'. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09628436
- Volume :
- 378
- Issue :
- 1879
- Database :
- Complementary Index
- Journal :
- Philosophical Transactions of the Royal Society B: Biological Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 163438069
- Full Text :
- https://doi.org/10.1098/rstb.2022.0163