So little source, so much sink: Requirements for afterdepolarizations to propagate in tissue

Yuanfang Xie, Daisuke Sato, Alan Garfinkel, Zhilin Qu, James N. Weiss

Research output: Contribution to journalArticle

172 Citations (Scopus)

Abstract

How early (EADs) and delayed after depolarizations (DADs) overcome electrotonic source-sink mismatches in tissue to trigger premature ventricular complexes remains incompletely understood. To study this question, we used a rabbit ventricular action potential model to simulate tissues in which a central area of contiguous myocytes susceptible to EADs or DADs was surrounded by unsusceptible tissue. In 1D tissue with normal longitudinal conduction velocity (0.55 m/s), the numbers of contiguous susceptible myocytes required for an EAD and a barely suprathreshold DAD to trigger a propagating action potential were 70 and 80, respectively. In 2D tissue, these numbers increased to 6940 and 7854, and in 3D tissue to 696,910 and 817,280. These numbers were significantly decreased by reduced gap junction conductance, simulated fibrosis, reduced repolarization reserve and heart failure electrical remodeling. In conclusion, the source-sink mismatch in well-coupled cardiac tissue powerfully protects the heart from arrhythmias due to sporadic afterdepolarizations. Structural and electrophysiological remodeling decrease these numbers significantly but still require synchronization mechanisms for EADs and DADs to overcome the robust protective effects of source-sink mismatch.

Original languageEnglish (US)
Pages (from-to)1408-1415
Number of pages8
JournalBiophysical Journal
Volume99
Issue number5
DOIs
StatePublished - Sep 8 2010

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Muscle Cells
Action Potentials
Atrial Remodeling
Ventricular Premature Complexes
Gap Junctions
Cardiac Arrhythmias
Fibrosis
Heart Failure
Rabbits

ASJC Scopus subject areas

  • Biophysics

Cite this

So little source, so much sink : Requirements for afterdepolarizations to propagate in tissue. / Xie, Yuanfang; Sato, Daisuke; Garfinkel, Alan; Qu, Zhilin; Weiss, James N.

In: Biophysical Journal, Vol. 99, No. 5, 08.09.2010, p. 1408-1415.

Research output: Contribution to journalArticle

Xie, Yuanfang ; Sato, Daisuke ; Garfinkel, Alan ; Qu, Zhilin ; Weiss, James N. / So little source, so much sink : Requirements for afterdepolarizations to propagate in tissue. In: Biophysical Journal. 2010 ; Vol. 99, No. 5. pp. 1408-1415.
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