title: Selective sinoatrial node optical mapping and the mechanism of sinus rate acceleration.
abstract: BACKGROUND
  Studies using isolated sinoatrial node (SAN) cells indicate that rhythmic spontaneous sarcoplasmic reticulum calcium release (Ca clock) plays an important role in SAN automaticity. In the intact SAN, cross-contamination of optical signals from the SAN and the right atrium (RA) prevent the definitive testing of Ca clock hypothesis. The aim of this study was to use a novel approach to selectively mapping the intact SAN to examine the Ca clock mechanism.
  
  
  RESULTS
  We simultaneously mapped intracellular Ca (Ca(i)) and membrane potential (V(m)) in 10 isolated, Langendorff-perfused normal canine RAs. The excitability of the RA was suppressed with high-potassium Tyrode's solution, allowing selective optical mapping of V(m) and Ca(i) of the SAN. Isoproterenol (ISO, 0.03 µmol/L) decreased the cycle length of the sinus beats, and shifted the leading pacemaker site from the middle or inferior SAN to the superior SAN in all RAs. The Ca(i) upstroke preceded the V(m) in the leading pacemaker site by up to 18 ± 2 ms. ISO-induced changes to SAN were inhibited by ryanodine (3 µmol/L), but not ZD7288 (3 µmol/L), a selective I(f) blocker.
  
  
  CONCLUSIONS
  We conclude that, in the isolated canine RA, a high extracellular potassium concentration can suppress atrial excitability thus leading to SAN-RA conduction block, allowing selective optical mapping of the intact SAN. Acceleration of Ca cycling in the superior SAN underlies the mechanism of sinus tachycardia during sympathetic stimulation.
authors.affiliation: The Krannert Institute of Cardiology, Indianapolis, IN, USA.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Shinohara
authors.forename: Hyung-Wook
authors.initials: HW
authors.lastname: Park
authors.forename: Boyoung
authors.initials: B
authors.lastname: Joung
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Maruyama
authors.forename: Su-Kiat
authors.initials: SK
authors.lastname: Chua
authors.forename: Seongwook
authors.initials: S
authors.lastname: Han
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Shen
authors.forename: Peng-Sheng
authors.initials: PS
authors.lastname: Chen
authors.forename: Shien-Fong
authors.initials: SF
authors.lastname: Lin
mesh_terms: D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000493:pharmacokinetics*; D002316:Cardiotonic Agents / Q000494:pharmacology; D004285:Dogs; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006947:Hyperkalemia / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology; D007552:Isotonic Solutions / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D010477:Perfusion; D011188:Potassium / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000502:physiology; D012849:Sinoatrial Node / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D013616:Tachycardia, Sinus / Q000503:physiopathology*
chemical_list: D002316:Cardiotonic Agents; D007552:Isotonic Solutions; D011743:Pyrimidines; C037692:Tyrode's solution; C082246:ICI D2788; D012433:Ryanodine; D007545:Isoproterenol; D011188:Potassium; D002118:Calcium
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