Arrhythmias & electrophysiology
Downregulation of L-type Ca2+ current in patients with atrial fibrillation results from altered channel gating and disruption of membrane microdomains
Authors' conclusion
ICa,L downregulation in AF is driven by chamber-specific degradation of membrane structures and loss of functional LTCCs, not offset by increased channel activity. Caveolin-3 is crucial for maintaining functional LTCCs at the sarcolemma.
Study context
- Population
- Patients in sinus rhythm and patients with chronic atrial fibrillation; right atrial and left atrial biopsiesSinus rhythm (SR) n = 51, AF n = 61
- Participants
- 61 vs 51
- Comparison
- AF vs SR, right atrial and left atrial biopsies
- AFn = 61
- SRn = 51
- Outcome
- ICa,L
Main finding
As reported in the abstract
ICa,L reduced in AF in right atrial (RA)
∼32%
P < .05
ICa,L reduced in AF in left atrial (LA)
∼71%
P < .01
Further findings
LTCC density
- RA: preserved tubular LTCCs (T-LTCCs) density, decreased C-LTCCs density
- LA-AF: densities of both T- and C-LTCCs reduced
- T-tubule downregulation in both atria and LA-specific decrease in caveolin-3 expression
Open probability of T- and C-LTCCs
- In AF, open probabilities in both atria higher than in SR
- 3-5-fold
- Increase in protein kinase A and phosphorylated Ca2+/calmodulin kinase II activities
- 2-fold
Computational simulations
- Enhanced LTCC open probability did not compensate for reduced channel density
Caveolin-3 overexpression in LA-AF cardiomyocytes
- Increased CaV1.2 membrane expression, partially restoring ICa,L
Original publication
Downregulation of L-type Ca2+ current in patients with atrial fibrillation results from altered channel gating and disruption of membrane microdomains. Heart Rhythm. Published 1 April 2026. doi:10.
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