Arrhythmias & electrophysiology
Phosphodiesterase 8 governs cAMP/PKA-dependent reduction of L-type calcium current in human atrial fibrillation: a novel arrhythmogenic mechanism
Authors' conclusion
Both PDE8A and PDE8B are expressed in human heart. Upregulation of PDE8B isoforms in cAF reduces ICa,L via direct interaction of PDE8B2 with the Cav1.2α1C subunit.
Study context
- Population
- Patients with atrial fibrillation (AF) or sinus rhythm (human atrial myocytes)
- Comparison
- cAF and paroxysmal AF (pAF) vs sinus rhythm
- Outcome
- Contribution of altered PDE8 isoform function to reduced L-type Ca2+ current (ICa,L) in cAF
Main finding
As reported in the abstract
- PDE8A gene and protein levels higher in pAF vs sinus rhythm (SR)
- PDE8B upregulated in cAF only
- Cytosolic PDE8A higher in pAF myocytes; PDE8B tended to be more abundant at plasmalemma in cAF myocytes
- Only PDE8B2 bound Cav1.2α1C subunit; binding strongly increased in cAF
- Lower Cav1.2α1C Ser1928 phosphorylation with decreased ICa,L in cAF
- Selective PDE8 inhibition increased Ser1928 phosphorylation, enhanced subsarcolemmal cAMP and rescued lower ICa,L in cAF, with prolonged action potential duration at 50% repolarization
Original publication
Phosphodiesterase 8 governs cAMP/PKA-dependent reduction of L-type calcium current in human atrial fibrillation: a novel arrhythmogenic mechanism. Eur Heart J. Published 22 February 2023. doi:10.
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