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Dyssynchronous calcium removal in heart failure-induced atrial remodeling
- Source :
- American Journal of Physiology-Heart and Circulatory Physiology. 311:H1352-H1359
- Publication Year :
- 2016
- Publisher :
- American Physiological Society, 2016.
-
Abstract
- We tested the hypothesis that in atrial myocytes from a rabbit left ventricular heart failure (HF) model, spatial inhomogeneity and temporal dyssynchrony of Ca removal during excitation-contraction coupling together with increased Na/Ca exchange (NCX) activity generate a substrate for proarrhythmic Ca release. Ca removal occurs via Ca reuptake into the sarcoplasmic reticulum and extrusion via NCX exclusively in the cell periphery since rabbit atrial myocytes lack transverse tubules. Ca removal kinetics were assessed by the time constant τ of decay of local peripheral subsarcolemmal (SS) and central (CT) action potential (AP)-induced Ca transients (CaTs) recorded in confocal line scan mode (using Fluo-4). Spatial and temporal dyssynchrony of Ca removal was quantified by CV TAU, defined as the standard deviation of local τ along the transverse cell axis divided by mean τ. In normal cells CT CaT decline was slower compared with the SS domain, while in HF cells decline was accelerated, became equal in SS and CT regions, and a significant increase of CV TAU indicated an increased Ca removal dyssynchrony. In HF atrial cells NCX upregulation was accompanied by an overall higher incidence of spontaneous Ca waves and a higher propensity of arrhythmogenic Ca waves, defined as waves that triggered APs due to NCX-mediated membrane depolarization. NCX inhibition normalized CV TAU in HF atrial cells and decreased the propensity of Ca waves. In summary, HF atrial myocytes show accelerated but dyssynchronous diastolic Ca removal and altered sarcoplasmic reticulum Ca-ATPase (SERCA) and NCX activity that result in increased susceptibility to arrhythmia.
- Subjects :
- Male
0301 basic medicine
medicine.medical_specialty
SERCA
Physiology
Diastole
Action Potentials
chemistry.chemical_element
030204 cardiovascular system & hematology
Calcium
Sodium-Calcium Exchanger
Sarcoplasmic Reticulum Calcium-Transporting ATPases
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Physiology (medical)
Internal medicine
medicine
Animals
Myocytes, Cardiac
Heart Atria
Excitation Contraction Coupling
Heart Failure
CATS
Cardiac Excitation and Contraction
Endoplasmic reticulum
Depolarization
Atrial Remodeling
medicine.disease
Sarcoplasmic Reticulum
030104 developmental biology
Endocrinology
chemistry
Heart failure
Cardiology
Rabbits
Cardiology and Cardiovascular Medicine
Subjects
Details
- ISSN :
- 15221539 and 03636135
- Volume :
- 311
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Heart and Circulatory Physiology
- Accession number :
- edsair.doi.dedup.....c2c1d253a25ad58e7beaa2a5da12b19a