Delayed afterdepolarization in intact canine sinoatrial node as a novel mechanism for atrial arrhythmia

Boyoung Joung, Hong Zhang, Tetsuji Shinohara, Mitsunori Maruyama, Seongwook Han, Daehyeok Kim, Eue Keun Choi, Young Keun On, Shien-Fong Lin, Peng Sheng Chen*

*Corresponding author for this work

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Delayed Afterdepolarization in Sinoatrial Node. Introduction: Recent evidence indicates that spontaneous sarcoplasmic reticulum Ca release and Na-Ca exchanger current activation contribute to the sinoatrial node (SAN) automaticity. These findings suggest that SAN activity may share mechanisms that underlie both automaticity and triggered activity. The aim of this study is to test the hypothesis that spontaneous, nonvoltage gated, intracellular Ca (Ca i ) elevation may induce delayed afterdepolarization (DAD) in intact SAN during isoproterenol infusion. Methods and Results: We simultaneously mapped Ca i and membrane potential in 31 isolated Langendorff-perfused canine right atriums (RA). Isoproterenol increased heart rate and late diastolic Ca i elevation (LDCAE) of the superior SAN, leading to consistent SAN automaticity in all 31 RAs. However, DAD-like diastolic depolarizations (DD) were transiently observed in 4 RAs during isoproterenol infusion. These DAD-like DDs were preceded by LDCAE, but did not trigger a full action potential. The LDCAE preceding DAD-like DDs had smaller amplitude (0.41 ± 0.08 AU vs 0.48 ± 0.07 AU, P = 0.001) and less steep slopes (3.7 ± 1.3 AU/s vs 4.8 ± 1.4 AU/s, P = 0.001) than that of sinus beats. The coupling interval of DAD-like DDs was longer than that of the preceding normal beats (407 ± 48 ms vs 371 ± 44 ms, P = 0.002). Conclusion: The isoproterenol-induced LDCAE of superior SAN induced a full action potential in most cases. However, if the LDCAE was too small to trigger an action potential, then it induces only DAD-like DD. The failure of DAD-like DD to consistently trigger a sinus beat is a novel mechanism of atrial arrhythmogenesis.

Original languageEnglish
Pages (from-to)448-454
Number of pages7
JournalJournal of Cardiovascular Electrophysiology
Volume22
Issue number4
DOIs
StatePublished - 1 Apr 2011

Keywords

  • afterdepolarization
  • calcium dynamics
  • sinoatrial node
  • sympathetic nervous system
  • triggered activity

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