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

Research output: Contribution to journalJournal articleResearchpeer-review

  • Gary L Aistrup
  • Rishi Arora
  • Grubb, Søren
  • Shin Yoo
  • Benjamin Toren
  • Manvinder Kumar
  • Aaron Kunamalla
  • William Marszalec
  • Tej Motiwala
  • Shannon Tai
  • Sean Yamakawa
  • Satya Yerrabolu
  • Francisco J Alvarado
  • Hector H Valdivia
  • Jonathan M Cordeiro
  • Yohannes Shiferaw
  • John Andrew Wasserstrom

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.

Original languageEnglish
JournalCardiovascular Research
Issue number13
Pages (from-to)1688-1699
Number of pages12
Publication statusPublished - 1 Nov 2017
Externally publishedYes

    Research areas

  • Journal Article

ID: 188527272