Ionic mechanisms underlying region-specific remodeling of rabbit atrial action potentials caused by intermittent burst stimulation

Wen Dun, Nazira Özgen, Masanori Hirose, Eugene A. Sosunov, Evgeny P. Anyukhovsky, Michael R. Rosen, Penelope A. Boyden

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

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 (Ito) and sustained (Isus) K+ currents as well as Ca2+ currents (ICa) 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 Ca2+ channel subunit mRNAs to determine if intermittent burst pacing affected expression levels. Results: Ito densities were unaffected by intermittent burst pacing in PV and Bachmann bundle cells. mRNA levels of KV4.3, KV4.2, KV1.4, and KChIP2 subunits of Ito in both regions were stable. In CS cells, Ito densities in intermittent burst pacing were greater than in sham (P <.05), but there were no parallel mRNA changes. ICa 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 α1C and α1D Ca2+ channel subunits. In contrast, intermittent burst pacing had no effect on Ca2+ current densities and kinetics of CS cells, but decreased α1C and α1D mRNA levels. Conclusion: There is region-specific remodeling of Ito and ICa by intermittent burst pacing protocols in rabbit atrium. Increased Ito 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.

Original languageEnglish
Pages (from-to)499-507
Number of pages9
JournalHeart Rhythm
Volume4
Issue number4
DOIs
Publication statusPublished - 2007 Apr

Keywords

  • Atrial fibrillation
  • Ionic currents
  • Pacing
  • Remodeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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