Heart Rate Acceleration of Subsidiary Pacemaker by β-Adrenergic Stimulation

Boyoung Joung, Hyerim Park, Jaemin Shim, Jaesun Um, Hyejin Hwang, Jong Youn Kim, Hui Nam Pak, Moon Hyoung Lee

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Backgrounds: The membrane voltage and Ca2+ clocks jointly regulate sinoatrial node (SAN) automaticity. Here we test the hypothesis that heart rate acceleration of subsidiary pacemaker (SP) by β-adrenergic stimulation involves synergistic interactions between both clock mechanisms. Methods: We performed optical mapping and pharmacological interventions in 15 isolated Langendorff-perfused canine right atriums (RA). SP model were produced by ligation of SAN artery at the mid portion of sulcus terminalis. Results: In 6 RAs with intact SAN, isoproterenol infusion of 1 μ/mol/L increased heart rate from 82±9 to 166± 18 bpm (102%) with late diastolic Cai elevation (LDCAE) at superior SAN. However, in 6 SP models, heart rate increased from 55± 10 bpm to 106± 11 bpm (92%, p=0.005) without LDCAE at the earliest activation site. The isoproterenol induced heart rate increase was reversed to 74±5 bpm (33% from baseline) by funny current blocker, ZD 7288 infusion (3 ±mol/L, n=3). Whereas, it was suppressed to 69±7 bpm (24% from baseline) by SR Ca2+ emptying with ryanodine (10 ±mol/L) plus thapsigargin (200 nmol/L, n=3). The isoproterenol induced heart rate increase was completely abolished by combined funny current blocker and SR Ca2+ emptying (n=3). Conclusion: Acceleration of the Ca2+ clock in SP plays an important role in heart rate acceleration during β-adrenergic stimulation, interacting synergistically with the voltage clock to increase heart rate.

Original languageEnglish
Number of pages1
JournalJournal of Arrhythmia
Issue number4
Publication statusPublished - 2011 Jan 1
Externally publishedYes


  • calcium clock
  • membrane clock
  • subsidiary pacemaker

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Joung, B., Park, H., Shim, J., Um, J., Hwang, H., Kim, J. Y., Pak, H. N., & Lee, M. H. (2011). Heart Rate Acceleration of Subsidiary Pacemaker by β-Adrenergic Stimulation. Journal of Arrhythmia, 27(4). https://doi.org/10.4020/jhrs.27.BPB_3