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  • Title: Ionic mechanisms underlying region-specific remodeling of rabbit atrial action potentials caused by intermittent burst stimulation.
    Author: Dun W, Ozgen N, Hirose M, Sosunov EA, Anyukhovsky EP, Rosen MR, Boyden PA.
    Journal: Heart Rhythm; 2007 Apr; 4(4):499-507. PubMed ID: 17399641.
    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. CONCLUSION: 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.
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