Unique topographical distribution of M cells underlies reentrant mechanism of torsade de pointes in the long-QT syndrome

Fadi G. Akar, Gan Xin Yan, Charles Antzelevitch, David S. Rosenbaum

Research output: Contribution to journalArticlepeer-review

Abstract

Background - Specific ion channel mutations underlie the congenital long-QT syndrome (LQTS). However, the mechanisms by which dysfunction at the molecular level translates into functional electrical instability leading to torsade de pointes (TdP) in LQTS are poorly understood. Methods and Results - The cellular basis of TdP was investigated using a novel approach of transmural optical imaging in the canine wedge preparation (n= 14). The spatial organization of repolarization and arrhythmogenesis were determined in a surrogate model of LQT2. Action potentials were recorded simultaneously from 128 sites spanning the transmural wall of the left ventricle. In LQT2, QT interval prolongation was paralleled by an abrupt rise in transmural dispersion of repolarization (DOR) from 2.7±0.9 ms/mm (controls) to 12.2±2.1 ms/mm (LQT2). Islands of midmyocardial (M) cells formed zones of increased refractoriness in LQT2, producing steep spatial gradients of repolarization that were directly responsible for conduction block and self-sustained intramural reentrant circuits underlying TdP. Conclusions - These data provide direct evidence supporting the functional expression of M cells in intact myocardium and a central role for M cells in the development of reentrant TdP arrhythmias in LQTS.

Original languageEnglish (US)
Pages (from-to)1247-1253
Number of pages7
JournalCirculation
Volume105
Issue number10
DOIs
StatePublished - Mar 12 2002

Keywords

  • Action potentials
  • Arrhythmia
  • Ion channels
  • Mapping
  • Torsades de pointes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Unique topographical distribution of M cells underlies reentrant mechanism of torsade de pointes in the long-QT syndrome'. Together they form a unique fingerprint.

Cite this