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Heart Rate Acceleration of a Subsidiary Pacemaker by β-Adrenergic Stimulation

Authors
 Sanghoon Park  ;  Hyerim Park  ;  Hye Jin Hwang  ;  Jaemin Shim  ;  Jung-Hoon Sung  ;  Jong-Youn Kim  ;  Hui-Nam Pak  ;  Moon-Hyoung Lee  ;  Boyoung Joung 
Citation
 KOREAN CIRCULATION JOURNAL, Vol.41(11) : 658-665, 2011 
Journal Title
KOREAN CIRCULATION JOURNAL
ISSN
 1738-5520 
Issue Date
2011
Keywords
Calcium channel ; Sympathetic nervous system ; Sinoatrial node
Abstract
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.

SUBJECTS 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(i) 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.
Files in This Item:
T201105011.pdf Download
DOI
10.4070/kcj.2011.41.11.658
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jong Youn(김종윤) ORCID logo https://orcid.org/0000-0001-7040-8771
Pak, Hui Nam(박희남) ORCID logo https://orcid.org/0000-0002-3256-3620
Shim, Jae Min(심재민)
Lee, Moon-Hyoung(이문형) ORCID logo https://orcid.org/0000-0002-7268-0741
Joung, Bo Young(정보영) ORCID logo https://orcid.org/0000-0001-9036-7225
Hwang, Hye Jin(황혜진)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/94890
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