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Cardiovasc Res. 2017 Nov 1;113(13):1688-1699. doi: 10.1093/cvr/cvx167.

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

Author information

1
Department of Medicine (Cardiology) and the Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
2
The Center for Arrhythmia Research, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
3
Masonic Medical Research Laboratory, Utica, NY 13501, USA.
4
Department of Physics, California State University Northridge, Northridge, CA 91330, USA.

Abstract

Aims:

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.

Methods and results:

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.

Conclusion:

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.

KEYWORDS:

Atrial fibrillation; Atrium; Heart failure;  Ca2+ waves

PMID:
29016724
PMCID:
PMC5852523
DOI:
10.1093/cvr/cvx167
[Indexed for MEDLINE]
Free PMC Article

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