Early electrical remodeling in rabbit pulmonary vein results from trafficking of intracellular SK2 channels to membrane sites

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

Research output: Contribution to journalArticlepeer-review

99 Citations (Scopus)

Abstract

Objective: Atrial fibrillation is often initiated by bursts of ectopic activity arising in the pulmonary veins. We have previously shown that a 3-h intermittent burst pacing protocol (BPP), mimicking ectopic pulmonary vein foci, shortens action potential duration (APD) locally at the pulmonary vein-atrial interface (PV) while having no effect elsewhere in rabbit atrium. This shortening is Ca2+ dependent and is prevented by apamin, which blocks small conductance Ca2+-activated K+ channels (SKCa). The present study investigates the ionic and molecular mechanisms whereby two apamin-sensitive SKCa channels, SK2 and SK3, might contribute to the regional APD changes. Methods: Microelectrode and patch clamp techniques were used to record APDs and apamin-sensitive currents in isolated rabbit left atria and cells dispersed from PV and Bachmann's bundle (BB) regions. SK2 and SK3 mRNA and protein levels were quantified, and immunofluorescence was used to observe channel protein distribution. Results: There was a direct relationship between APD shortening and apamin-sensitive current in burst-paced but not sham-paced PV. Moreover, apamin-sensitive current density increased in PV but not BB after BPP. SK2 mRNA, protein, and current were increased in PV after BPP, while SK2 immunostaining shifted from a perinuclear pattern in sham atria to predominance at sites near or at the PV membrane. Conclusions: BPP-induced acceleration of repolarization in PV results from SK2 channel trafficking to the membrane, leading to increased apamin-sensitive outward current. This is the first indication of involvement of Ca2+-activated K+ currents in atrial remodeling and provides a possible basis for evolution of an arrhythmogenic substrate.

Original languageEnglish
Pages (from-to)758-769
Number of pages12
JournalCardiovascular Research
Volume75
Issue number4
DOIs
Publication statusPublished - 2007 Sep 1

Keywords

  • Arrhythmias
  • Ion channels
  • K channels

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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