TY - JOUR
T1 - Irregularly appearing early afterdepolarizations in cardiac myocytes
T2 - Random fluctuations or dynamical chaos?
AU - Sato, Daisuke
AU - Xie, Lai Hua
AU - Nguyen, Thao P.
AU - Weiss, James N.
AU - Qu, Zhilin
N1 - Funding Information:
This work was supported by a grant from the National Institutes of Health/National Heart, Lung, and Blood Institute (P01 HL078931), a postdoctoral fellowship award from the American Heart Association, Western States Affiliate (to D.S.), and the Laubisch and Kawata Endowments.
PY - 2010/8/4
Y1 - 2010/8/4
N2 - Irregularly occurring early afterdepolarizations (EADs) in cardiac myocytes are traditionally hypothesized to be caused by random ion channel fluctuations. In this study, we combined 1), patch-clamp experiments in which action potentials were recorded at different pacing cycle lengths from isolated rabbit ventricular myocytes under several experimental conditions inducing EADs, including oxidative stress with hydrogen peroxide, calcium overload with BayK8644, and ionic stress with hypokalemia; 2), computer simulations using a physiologically detailed rabbit ventricular action potential model, in which repolarization reserve was reduced to generateEADs and randomion channel or path cycle length fluctuationswere implemented; and 3), iterated mapswith or without noise.Bycomparing experimental,modeling, and bifurcation analyses,wepresent evidence thatnoise-induced transitions between bistable states (i.e., between an action potential with and without an EAD) is not sufficient to account for the large variation in action potential duration fluctuations observed in experimental studies. We conclude that the irregular dynamics of EADs is intrinsically chaotic, with random fluctuations playing a nonessential, auxiliary role potentiating the complex dynamics.
AB - Irregularly occurring early afterdepolarizations (EADs) in cardiac myocytes are traditionally hypothesized to be caused by random ion channel fluctuations. In this study, we combined 1), patch-clamp experiments in which action potentials were recorded at different pacing cycle lengths from isolated rabbit ventricular myocytes under several experimental conditions inducing EADs, including oxidative stress with hydrogen peroxide, calcium overload with BayK8644, and ionic stress with hypokalemia; 2), computer simulations using a physiologically detailed rabbit ventricular action potential model, in which repolarization reserve was reduced to generateEADs and randomion channel or path cycle length fluctuationswere implemented; and 3), iterated mapswith or without noise.Bycomparing experimental,modeling, and bifurcation analyses,wepresent evidence thatnoise-induced transitions between bistable states (i.e., between an action potential with and without an EAD) is not sufficient to account for the large variation in action potential duration fluctuations observed in experimental studies. We conclude that the irregular dynamics of EADs is intrinsically chaotic, with random fluctuations playing a nonessential, auxiliary role potentiating the complex dynamics.
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U2 - 10.1016/j.bpj.2010.05.019
DO - 10.1016/j.bpj.2010.05.019
M3 - Article
C2 - 20682253
AN - SCOPUS:77955688268
SN - 0006-3495
VL - 99
SP - 765
EP - 773
JO - Biophysical Journal
JF - Biophysical Journal
IS - 3
ER -