Induction of atrial ectopic beats with calcium release inhibition: Local hierarchy of automaticity in the right atrium

Tetsuji Shinohara, Boyoung Joung, Daehyeok Kim, Mitsunori Maruyama, Hsiang Ning Luk, Peng Sheng Chen, Shien Fong Lin

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


Background: Recent evidence indicates that spontaneous sarcoplasmic reticulum (SR) calcium (Ca) release underlies the mechanism of sinoatrial node (SAN) acceleration during β-stimulation, indicating the importance of the Ca clock in SAN automaticity. Whether or not the same mechanism applies to atrial ectopic pacemakers (AEPs) remains unclear. Objective: The purpose of this study was to assess the mechanism of AEP. Methods: We simultaneously mapped intracellular calcium (Cai) and membrane potential in 12 isolated canine right atria. The late diastolic Cai elevation (LDCAE) was used to detect the Ca clock activity. Pharmacological interventions with isoproterenol (ISO), ryanodine, and ZD7288, a blocker of the If membrane current, were performed. Results: Ryanodine, which inhibits SR Ca release, reduced LDCAE in SAN, resulting in an inferior shift of the pacemaking site. Cycle length increased significantly in a dose-dependent way. In the presence of 3 to 10 μmol/l of ryanodine, ISO infusion consistently induces AEPs from the lower crista terminalis. All ectopic beats continuing over 30 seconds were located at the lower crista terminalis. These AEPs were resistant to ryanodine treatment even at high doses. Subsequent blockade of If inhibited the AEP and resulted in profound bradycardia. Conclusion: Spontaneous SR Ca release underlies ISO-induced increase of superior SAN activity. As compared with SAN, the AEP is less dependent on the Ca clock and more dependent on the membrane clock for its automaticity. AEPs outside the SAN can effectively serve as backup pacemakers when the Ca clock functionality is reduced.

Original languageEnglish
Pages (from-to)110-116
Number of pages7
JournalHeart Rhythm
Issue number1
Publication statusPublished - 2010 Jan

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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