Heart rate acceleration of a subsidiary pacemaker by β-adrenergic stimulation

Sanghoon Park, Hyerim Park, Hye Jin Hwang, Jaemin Shim, Jung Hoon Sung, Jong Youn Kim, Hui Nam Pak, Moon Hyoung Lee, Boyoung Joung

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2 Citations (Scopus)


Background and Objectives: Recent evidence indicates that the membrane voltage and Ca 2+ clocks jointly regulate sinoatrial node (SAN) automaticity. However, the mechanism of heart rhythm acceleration of the subsidiary pacemaker (SP) during β-adrenergic stimulation is still unknown. Here we tested the hypothesis that the heart rate acceleration of the SP by β-adrenergic stimulation involves synergistic interactions between both clock mechanisms. Materials and Methods: We performed optical mapping and pharmacological interventions in 15 isolated Langendorff-perfused canine right atriums (RA). The SP model was produced by ligation of the SAN artery at the mid portion of the sulcus terminalis. Results: In the 6 RAs with an intact SAN, 1 μmol/L isoproterenol infusion increased the heart rate from 82±9 to 166±18 bpm (102%) with late diastolic Ca 1 elevation (LDCAE) at the superior SAN. However, in the 6 SP models, the 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 administering an infusion of the funny current blocker ZD 7288 (3 μmol/L, n=3), whereas, it was suppressed to 69±7 bpm (24% from baseline) by sarcoplasmic reticulum (SR) Ca 2+ emptying with administering ryanodine (10 μmol/L) plus thapsigargin (200 nmol/L, n=3). The isoproterenol induced heart rate increase was completely abolished by combined treatment with funny current blocker and SR Ca 2+ emptying (n=3). Conclusion: Acceleration of the Ca 2+ clock in the SP plays an important role in the heart rate acceleration during β-adrenergic stimulation, and this interacts synergistically with the voltage clock to increase the heart rate.

Original languageEnglish
Pages (from-to)658-665
Number of pages8
JournalKorean Circulation Journal
Issue number11
Publication statusPublished - 2011 Nov 1
Externally publishedYes


  • Calcium channel
  • Sinoatrial node
  • Sympathetic nervous system

ASJC Scopus subject areas

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine

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    Park, S., Park, H., Hwang, H. J., Shim, J., Sung, J. H., Kim, J. Y., Pak, H. N., Lee, M. H., & Joung, B. (2011). Heart rate acceleration of a subsidiary pacemaker by β-adrenergic stimulation. Korean Circulation Journal, 41(11), 658-665. https://doi.org/10.4070/kcj.2011.41.11.658