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

    Research output: Contribution to journalArticlepeer-review

    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


    • Calcium channel
    • Sinoatrial node
    • Sympathetic nervous system

    ASJC Scopus subject areas

    • Internal Medicine
    • Cardiology and Cardiovascular Medicine


    Dive into the research topics of 'Heart rate acceleration of a subsidiary pacemaker by β-adrenergic stimulation'. Together they form a unique fingerprint.

    Cite this