Mechanism for Triggered Waves in Atrial Myocytes.

Abstract:

:Excitation-contraction coupling in atrial cells is mediated by calcium (Ca) signaling between L-type Ca channels and Ryanodine receptors that occurs mainly at the cell boundary. This unique architecture dictates essential aspects of Ca signaling under both normal and diseased conditions. In this study we apply laser scanning confocal microscopy, along with an experimentally based computational model, to understand the Ca cycling dynamics of an atrial cell subjected to rapid pacing. Our main finding is that when an atrial cell is paced under Ca overload conditions, Ca waves can then nucleate on the cell boundary and propagate to the cell interior. These propagating Ca waves are referred to as "triggered waves" because they are initiated by L-type Ca channel openings during the action potential. These excitations are distinct from spontaneous Ca waves originating from random fluctuations of Ryanodine receptor channels, and which occur after much longer waiting times. Furthermore, we argue that the onset of these triggered waves is a highly nonlinear function of the sarcoplasmic reticulum Ca load. This strong nonlinearity leads to aperiodic response of Ca at rapid pacing rates that is caused by the complex interplay between paced Ca release and triggered waves. We argue further that this feature of atrial cells leads to dynamic instabilities that may underlie atrial arrhythmias. These studies will serve as a starting point to explore the nonlinear dynamics of atrial cells and will yield insights into the trigger and maintenance of atrial fibrillation.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Shiferaw Y,Aistrup GL,Wasserstrom JA

doi

10.1016/j.bpj.2017.06.026

subject

Has Abstract

pub_date

2017-08-08 00:00:00

pages

656-670

issue

3

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(17)30676-8

journal_volume

113

pub_type

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