Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Lenaerts, I; Bito, V; Heinzel, FR; Driesen, RB; Holemans, P; D'hooge, J; Heidbüchel, H; Sipido, KR; Willems, R.
Ultrastructural and functional remodeling of the coupling between Ca2+ influx and sarcoplasmic reticulum Ca2+ release in right atrial myocytes from experimental persistent atrial fibrillation.
Circ Res. 2009; 105(9): 876-885.
Doi: 10.1161/CIRCRESAHA.109.206276
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- Co-authors Med Uni Graz
- Heinzel Frank
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- Abstract:
- RATIONALE: Persistent atrial fibrillation (AF) has been associated with structural and electric remodeling and reduced contractile function. Objective: To unravel mechanisms underlying reduced sarcoplasmic reticulum (SR) Ca(2+) release in persistent AF. METHODS: We studied cell shortening, membrane currents, and [Ca(2+)](i) in right atrial myocytes isolated from sheep with persistent AF (duration 129+/-39 days, N=16), compared to matched control animals (N=21). T-tubule density, ryanodine receptor (RyR) distribution, and local [Ca(2+)](i) transients were examined in confocal imaging. RESULTS: Myocyte shortening and underlying [Ca(2+)](i) transients were profoundly reduced in AF (by 54.8% and 62%, P<0.01). This reduced cell shortening could be corrected by increasing [Ca(2+)](i). SR Ca(2+) content was not different. Calculated fractional SR Ca(2+) release was reduced in AF (by 20.6%, P<0.05). Peak Ca(2+) current density was modestly decreased (by 23.9%, P<0.01). T-tubules were present in the control atrial myocytes at low density and strongly reduced in AF (by 45%, P<0.01), whereas the regular distribution of RyR was unchanged. Synchrony of SR Ca(2+) release in AF was significantly reduced with increased areas of delayed Ca(2+) release. Propagation between RyR was unaffected but Ca(2+) release at subsarcolemmal sites was reduced. Rate of Ca(2+) extrusion by Na(+)/Ca(2+) exchanger was increased. CONCLUSIONS: In persistent AF, reduced SR Ca(2+) release despite preserved SR Ca(2+) content is a major factor in contractile dysfunction. Fewer Ca(2+) channel-RyR couplings and reduced efficiency of the coupling at subsarcolemmal sites, possibly related to increased Na(+)/Ca(2+) exchanger, underlie the reduction in Ca(2+) release.
- Find related publications in this database (using NLM MeSH Indexing)
- Actin Cytoskeleton - metabolism
- Animals -
- Atrial Fibrillation - metabolism
- Atrial Function, Right -
- Calcium Channels, L-Type - metabolism
- Calcium Signaling -
- Disease Models, Animal -
- Electrophysiologic Techniques, Cardiac -
- Female -
- Glycogen - metabolism
- Heart Atria - metabolism
- Membrane Potentials -
- Myocardial Contraction -
- Myocytes, Cardiac - metabolism
- Ryanodine Receptor Calcium Release Channel - metabolism
- Sarcolemma - metabolism
- Sarcoplasmic Reticulum - metabolism
- Sheep -
- Sodium-Calcium Exchanger - metabolism
- Time Factors -
- Find related publications in this database (Keywords)
- atrial fibrillation
- sarcoplasmic reticulum
- Na+/Ca2+ exchange
- ryanodine receptor
- T-tubules