Increased abundance and activity of PDE8B2 in chronic AF may explain the reduced basal phosphorylation of key LTCC subunits, providing novel mechanistic insights into dysregulated calcium cycling in atrial fibrillation.
Atrial contractility is regulated by intracellular calcium levels; these reflect the balance of calcium influx, sequestration, and efflux. Beta-adrenergic activation with either norepinephrine (endogenous) or isoproterenol (pharmacological) increases the activity of adenylate cyclase, increasing cAMP levels and protein kinase A (PKA) activity. Degradation of cAMP is regulated by phosphodiesterases (PDEs). The phosphorylation state of relevant PKA targets, such as the L-type calcium channel (LTCC), the sarcoplasmic reticulum Ca2+-ATPase (SERCA2a), and myofilament proteins, is regulated by the balance of PKA activity and phosphatase activity. In patients with no history of atrial fibrillation (AF) or paroxysmal AF (pAF), basal phosphorylation of key LTCC subunits is higher than in atrial myocytes from patients with chronic (persistent) AF.14 Pavlidou et al.14 provide novel evidence that this is probably due to increased abundance and activity of phosphodiesterase isoform 8B, variant 2 (PDE8B2), in patients with chronic AF.
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Rennison et al. (2023) studied this question.
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