title: Ionic mechanisms underlying region-specific remodeling of rabbit atrial action potentials caused by intermittent burst stimulation.
abstract: BACKGROUND
  Pulmonary veins (PVs) and the coronary sinus (CS) play pivotal roles in triggering some episodes of atrial fibrillation. In isolated rabbit right or left atrial preparations, a 3-hour intermittent burst pacing protocol shortens action potential duration (APD) in CS and PV, but not in sinus node (SN) and left Bachmann bundle (BB) regions.
  
  
  OBJECTIVE
  The purpose of this study was to use patch clamp techniques to study the rapidly inactivating (I(to)) and sustained (I(sus)) K(+) currents as well as Ca(2+) currents (I(Ca)) in cells dispersed from intermittent burst pacing and sham PV, BB, CS, and SN regions to determine whether changes in these currents contributed to APD shortening.
  
  
  METHODS
  Real-time polymerase chain reaction was performed for transient outward K(+) and Ca(2+) channel subunit mRNAs to determine if intermittent burst pacing affected expression levels.
  
  
  RESULTS
  I(to) densities were unaffected by intermittent burst pacing in PV and Bachmann bundle cells. mRNA levels of K(V)4.3, K(V)4.2, K(V)1.4, and KChIP2 subunits of I(to) in both regions were stable. In CS cells, I(to) densities in intermittent burst pacing were greater than in sham (P <.05), but there were no parallel mRNA changes. I(Ca) density of PV cells was reduced from 14.27 +/- 2.08 pA/pF (at -5 mV) in sham to 7.52 +/- 1.65 pA/pF in intermittent burst pacing PV cells (P <.05) due to a significant shift in voltage dependence of activation. These results were seen in the absence of mRNA changes in alpha(1C) and alpha(1D) Ca(2+) channel subunits. In contrast, intermittent burst pacing had no effect on Ca(2+) current densities and kinetics of CS cells, but decreased alpha(1)C and alpha(1)D mRNA levels.
  
  
  CONCLUSIONS
  There is region-specific remodeling of I(to) and I(Ca) by intermittent burst pacing protocols in rabbit atrium. Increased I(to) in CS cells could account for the APD shortening observed with intermittent burst pacing, whereas an intermittent burst pacing-induced shift in voltage dependence of activation may contribute to APD shortening in PV cells.
authors.affiliation: Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Dun
authors.forename: Nazira
authors.initials: N
authors.lastname: Ozgen
authors.forename: Masanori
authors.initials: M
authors.lastname: Hirose
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Sosunov
authors.forename: Evgeny P
authors.initials: EP
authors.lastname: Anyukhovsky
authors.forename: Michael R
authors.initials: MR
authors.lastname: Rosen
authors.forename: Penelope A
authors.initials: PA
authors.lastname: Boyden
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D001281:Atrial Fibrillation / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D016275:Atrial Function / Q000187:drug effects; D002036:Bundle of His / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D015220:Calcium Channels / Q000378:metabolism*; D002304:Cardiac Pacing, Artificial; D003331:Coronary Vessels / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D006325:Heart Atria / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D051605:Kv Channel-Interacting Proteins / Q000378:metabolism; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D016133:Polymerase Chain Reaction; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D011667:Pulmonary Veins / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D011930:Reaction Time / Q000187:drug effects; D012107:Research Design; D012849:Sinoatrial Node / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology
chemical_list: D015220:Calcium Channels; D051605:Kv Channel-Interacting Proteins; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger