Abstract 18709: Increased Open Probability of L-type Calcium Channels Localized in T-tubules in Patients With Chronic Atrial Fibrillation: Role of Channel Subunits
Background: L-type calcium channels (LTCCs) play a key role in electrical remodeling during atrial fibrillation (AF). AF is associated with increased single LTCC activity and also accompanied by profound changes in myocyte microanatomy. However, it remains unknown how loss of structure affects the activity of LTCCs.
Objective: To determine the microdomain-specific location, characteristics and structural composition of LTCCs in myocytes isolated from human right atrium.
Methods: Scanning ion conductance and confocal microscopy were used to characterize surface topography and t-tubules (TTs) in myocytes collected from 22 patients with sinus rhythm (AF-) and 28 patients with AF (AF+). Super-resolution scanning patch-clamp was applied to identify LTCCs in subcellular microdomains. qPCR was used to determine mRNA levels of LTCCs forming subunits.
Results: The surface topography of myocytes was less organized in AF+ compared to AF- patients with Z-groove index: 0.39± 0.04 vs 0.56 ± 0.02, P<0.01, respectively. Also TTs density was lower in AF+ myocytes in comparison with AF- myocytes (2.48±1.11 vs 5.4±3.41, ns, respectively). LTCCs recorded in the TTs in AF+ cells had a lower amplitude compared to AF- myocytes (0.5± 0.06 pA vs 0.77±0.06 pA, P<0.01, respectively).
Open probability of LTCCs was 2.6-fold higher in AF+ cells. All α1C, β1, β2, β3 and β4 subunits showed transcriptional downregulation in AF+ samples.
Conclusion: Significant surface and intercellular structural degradation was shown in human atrial cells collected from AF+ patients. Also single LTCCs located in TTs in AF+ myocytes showed increased open probability and decreased amplitude which correlated with transcriptional downregulation of channel subunits in samples collected from patients with AF. This could underlie their arrhythmogenic phenotype.
Author Disclosures: M. Balycheva: None. A. Glukhov: None. S. Schobesberger: None. J.L. Sanchez-Alonso: None. F. Schultz: None. P. Punjabi: None. G. Faggian: None. J. Gorelik: None.
- © 2014 by American Heart Association, Inc.