Triggered intracellular calcium waves in dog and human left atrial myocytes from normal and failing hearts

Abnormal intracellular Ca2+ cycling contributes to triggered activity and arrhythmias in the heart. We investigated the properties and underlying mechanisms for systolic triggered Ca2+ waves in left atria from normal and failing dog hearts. Intracellular Ca2+ cycling was studied using confocal micro...

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Bibliographic Details
Published in:Cardiovascular research 2017-11, Vol.113 (13), p.1688-1699
Main Authors: Aistrup, Gary L, Arora, Rishi, Grubb, Søren, Yoo, Shin, Toren, Benjamin, Kumar, Manvinder, Kunamalla, Aaron, Marszalec, William, Motiwala, Tej, Tai, Shannon, Yamakawa, Sean, Yerrabolu, Satya, Alvarado, Francisco J, Valdivia, Hector H, Cordeiro, Jonathan M, Shiferaw, Yohannes, Wasserstrom, John Andrew
Format: Article
Language:English
Subjects:
Action Potentials
Animals
Anti-Arrhythmia Agents - pharmacology
Atrial Fibrillation - metabolism
Atrial Fibrillation - physiopathology
Atrial Fibrillation - prevention & control
Calcium - metabolism
Calcium Signaling - drug effects
Calcium-Calmodulin-Dependent Protein Kinase Type 2 - antagonists & inhibitors
Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism
Cardiac Pacing, Artificial
Disease Models, Animal
Dogs
Excitation Contraction Coupling
Heart Atria - drug effects
Heart Atria - metabolism
Heart Atria - physiopathology
Heart Failure - drug therapy
Heart Failure - metabolism
Heart Failure - physiopathology
Heart Rate
Humans
Myocardial Contraction
Myocytes, Cardiac - drug effects
Myocytes, Cardiac - metabolism
Original
Protein Kinase Inhibitors - pharmacology
Sus scrofa
Time Factors
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Summary:Abnormal intracellular Ca2+ cycling contributes to triggered activity and arrhythmias in the heart. We investigated the properties and underlying mechanisms for systolic triggered Ca2+ waves in left atria from normal and failing dog hearts. Intracellular Ca2+ cycling was studied using confocal microscopy during rapid pacing of atrial myocytes (36 °C) isolated from normal and failing canine hearts (ventricular tachypacing model). In normal atrial myocytes (NAMs), Ca2+ waves developed during rapid pacing at rates ≥ 3.3 Hz and immediately disappeared upon cessation of pacing despite high sarcoplasmic reticulum (SR) load. In heart failure atrial myocytes (HFAMs), triggered Ca2+ waves (TCWs) developed at a higher incidence at slower rates. Because of their timing, TCW development relies upon action potential (AP)-evoked Ca2+ entry. The distribution of Ca2+ wave latencies indicated two populations of waves, with early events representing TCWs and late events representing conventional spontaneous Ca2+ waves. Latency analysis also demonstrated that TCWs arise after junctional Ca2+ release has occurred and spread to non-junctional (cell core) SR. TCWs also occurred in intact dog atrium and in myocytes from humans and pigs. β-adrenergic stimulation increased Ca2+ release and abolished TCWs in NAMs but was ineffective in HFAMs making this a potentially effective adaptive mechanism in normals but potentially arrhythmogenic in HF. Block of Ca-calmodulin kinase II also abolished TCWs, suggesting a role in TCW formation. Pharmacological manoeuvres that increased Ca2+ release suppressed TCWs as did interventions that decreased Ca2+ release but these also severely reduced excitation-contraction coupling. TCWs develop during the atrial AP and thus could affect AP duration, producing repolarization gradients and creating a substrate for reentry, particularly in HF where they develop at slower rates and a higher incidence. TCWs may represent a mechanism for the initiation of atrial fibrillation particularly in HF.
ISSN:0008-6363
1755-3245
DOI:10.1093/cvr/cvx167