Adenosine-Induced Atrial FibrillationClinical Perspective: Localized Reentrant Drivers in Lateral Right Atria due to Heterogeneous Expression of Adenosine A1 Receptors and GIRK4 Subunits in the Human Heart

Ning Li, Thomas A. Csepe, Brian J. Hansen, Lidiya V. Sul, Anuradha Kalyanasundaram, Stanislav O. Zakharkin, Jichao Zhao, Avirup Guha, David R. Van Wagoner, Ahmet Kilic, Peter J. Mohler, Paul M. L. Janssen, Brandon J. Biesiadecki, John D. Hummel, Raul Weiss, Vadim V. Fedorov

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

Background: Adenosine provokes atrial fibrillation (AF) with a higher activation frequency in right atria (RA) versus left atria (LA) in patients, but the underlying molecular and functional substrates are unclear. We tested the hypothesis that adenosine-induced AF is driven by localized reentry in RA areas with highest expression of adenosine A1 receptor and its downstream GIRK (G protein-coupled inwardly rectifying potassium channels) channels (I K,Ado). Methods: We applied biatrial optical mapping and immunoblot mapping of various atrial regions to reveal the mechanism of adenosine-induced AF in explanted failing and nonfailing human hearts (n=37). Results: Optical mapping of coronary-perfused atria (n=24) revealed that adenosine perfusion (10-100 mol/L) produced more significant shortening of action potential durations in RA (from 290±45 to 239±41 ms, 17.3±10.4%; P
Original languageEnglish (US)
Pages (from-to)486-498
Number of pages13
JournalCirculation
Volume134
Issue number6
DOIs
StatePublished - Jul 2016

Keywords

  • G protein-coupled inwardly rectifying potassium channels
  • adenosine
  • atrial fibrillation
  • optical mapping
  • receptor, adenosine A1
  • tertiapin

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