title: Calcium dynamics and the mechanisms of atrioventricular junctional rhythm.
abstract: OBJECTIVE
  The purpose of this study was to test the hypothesis that rhythmic spontaneous sarcoplasmic reticulum calcium (Ca) release (the "Ca clock") plays an important role in atrioventricular junction (AVJ) automaticity.
  
  
  BACKGROUND
  The AVJ is a primary backup pacemaker to the sinoatrial node. The mechanisms of acceleration of AVJ intrinsic rate during sympathetic stimulation are unclear.
  
  
  METHODS
  We simultaneously mapped transmembrane potential and intracellular Ca in Langendorff-perfused canine AVJ preparations that did not contain sinoatrial node (n = 10).
  
  
  RESULTS
  Baseline AVJ rate was 37.5 +/- 4.0 beats/min. The wavefront from leading pacemaker site propagated first through the slow pathway, then the fast pathway and atria. There was no late diastolic Ca elevation (LDCAE) at baseline. Isoproterenol up to 3 micromol/l increased heart rate to 100 +/- 6.8 beats/min, concomitant with the appearance of LDCAE that preceded the phase 0 of action potential by 97.3 +/- 35.2 ms and preceded the onset of late diastolic depolarization by 23.5 +/- 3.5 ms. Caffeine also produced LDCAE and AVJ acceleration. The maximal slope of LDCAE and diastolic depolarization always colocalized with the leading pacemaker sites. Ryanodine markedly slowed the rate of spontaneous AVJ rhythm. Isoproterenol did not induce LDCAE in the presence of ryanodine. The I(f) blocker ZD 7288 did not prevent LDCAE or AVJ acceleration induced by isoproterenol (n = 2).
  
  
  CONCLUSIONS
  Isoproterenol and caffeine induced LDCAE and accelerated intrinsic AVJ rhythm. Consistent colocalization of the maximum LDCAE and the leading pacemaker sites indicates that the Ca clock is important to the intrinsic AVJ rate acceleration during sympathetic stimulation.
authors.affiliation: Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Krannert Institute of Cardiology, Indianapolis, Indiana, USA.
authors.forename: Daehyeok
authors.initials: D
authors.lastname: Kim
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Shinohara
authors.forename: Boyoung
authors.initials: B
authors.lastname: Joung
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Maruyama
authors.forename: Eue-Keun
authors.initials: EK
authors.lastname: Choi
authors.forename: Young Keun
authors.initials: YK
authors.lastname: On
authors.forename: Seongwook
authors.initials: S
authors.lastname: Han
authors.forename: Michael C
authors.initials: MC
authors.lastname: Fishbein
authors.forename: Shien-Fong
authors.initials: SF
authors.lastname: Lin
authors.forename: Peng-Sheng
authors.initials: PS
authors.lastname: Chen
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects / Q000502:physiology*; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D004285:Dogs; D007545:Isoproterenol / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
chemical_list: D000318:Adrenergic beta-Agonists; D012433:Ryanodine; D002110:Caffeine; D007545:Isoproterenol; D002118:Calcium
references.citation: Ann N Y Acad Sci. 2006 Oct;1080:178-206
references.pmid: 17132784
references.citation: Biophys J. 2001 Jan;80(1):516-30
references.pmid: 11159422
references.citation: Proc Biol Sci. 1994 Feb 22;255(1343):99-105
references.pmid: 8165231
references.citation: Circulation. 2009 Feb 17;119(6):788-96
references.pmid: 19188501
references.citation: Circulation. 1998 Jul 7;98(1):54-7
references.pmid: 9665060
references.citation: Circulation. 2000 Mar 7;101(9):1049-59
references.pmid: 10704174
references.citation: Cell Calcium. 2008 Dec;44(6):580-91
references.pmid: 18550162
references.citation: J Am Coll Cardiol. 1999 Aug;34(2):570-7
references.pmid: 10440175
references.citation: Circulation. 1999 Sep 21;100(12):1346-53
references.pmid: 10491381
references.citation: Acta Physiol Scand. 2000 Mar;168(3):393-401
references.pmid: 10712577
references.citation: Circulation. 1998 Jan 20;97(2):188-93
references.pmid: 9445172
references.citation: Circulation. 1994 May;89(5):2351-60
references.pmid: 8181161
references.citation: Circ Res. 2009 Apr 10;104(7):915-23
references.pmid: 19246679
references.citation: Circ Res. 2001 Jun 8;88(11):1189-95
references.pmid: 11397786
references.citation: Circ Res. 2001 Feb 16;88(3):E23-30
references.pmid: 11179207
references.citation: Am J Physiol Heart Circ Physiol. 2009 Mar;296(3):H594-615
references.pmid: 19136600
references.citation: Circulation. 1991 May;83(5):1738-53
references.pmid: 1850667
references.citation: J Electrocardiol. 2005 Oct;38(4 Suppl):121-5
references.pmid: 16226086
references.citation: Heart Rhythm. 2007 Oct;4(10):1326-35
references.pmid: 17905339