Delayed rectifier K currents have reduced amplitudes and altered kinetics in myocytes from infarcted canine ventricle

Jiang, Min; Cabo, Cándido; Yao, Jianan; Boyden, Penelope A.; Tseng, Gea‐Ny

doi:10.1016/s0008-6363(00)00159-0

Cited by 94 publications

(75 citation statements)

References 22 publications

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“…In the PIZ and normal myocardium, action potential dynamics were represented via a validated human-specific model (43). In the PIZ, specific modifications to this model were incorporated to represent electrophysiological remodeling observed in patch-clamped myocytes harvested from the infarct border zone: fast sodium current (I Na ) was decreased by 62% (44), L-type calcium current (I Ca,L ) was decreased by 68% (45), and delayed rectifier potassium currents (I Kr and I Ks ) were decreased by 80% and 70%, respectively (46). Consequently, the PIZ action potential differed from that in the normal myocardium: +16.1% duration, -42.2% upstroke velocity, and -42.8% amplitude.…”

Section: Methodsmentioning

confidence: 99%

Optogenetic defibrillation terminates ventricular arrhythmia in mouse hearts and human simulations

Bruegmann¹,

Boyle²,

Vogt³

et al. 2016

Journal of Clinical Investigation

149

168

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Section: Methodsmentioning

confidence: 99%

Optogenetic defibrillation terminates ventricular arrhythmia in mouse hearts and human simulations

Bruegmann¹,

Boyle²,

Vogt³

et al. 2016

Journal of Clinical Investigation

149

168

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“…The major currents that determine the action potential of cells isolated from the canine left ventricular epicardium have been measured in both normal and infarcted hearts (1,12,17,21,24,25). These currents include the Na ϩ current (INa), ICaL, transient outward K ϩ current (Ito), delayed rectifier K ϩ currents (IKr and IKs), inward rectifier K ϩ current (IK1), and Na ϩ /Ca 2ϩ exchanger current (INaCa).…”

Section: Single Cell Modelmentioning

confidence: 99%

Electrical remodeling of the epicardial border zone in the canine infarcted heart: a computational analysis

Cabo

Boyden

2003

American Journal of Physiology-Heart and Circulatory Physiology

101

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Cabo, Candido, and Penelope A. Boyden. Electrical remodeling of the epicardial border zone in the healing canine infarcted heart: a computational analysis. Am J Physiol Heart Circ Physiol 284: H372-H384, 2003. First published September 19, 2002 10.1152/ajpheart.00512.2002The density and kinetics of several ionic currents of cells isolated from the epicardial border zone of the infarcted heart (IZs) are markedly different from cells from the noninfarcted canine epicardium (NZs). To understand how these changes in channel function affect the action potential of the IZ cell as well as its response to antiarrhythmic agents, we developed a new ionic model of the action potential of a cell that survives in the infarct (IZ) and one of a normal epicardial cell (NZ) using formulations based on experimental measurements. The difference in action potential duration (APD) between NZ and IZ cells during steady-state stimulation (basic cycle length ϭ 250 ms) was 6 ms (156 ms in NZ and 162 ms in IZ). However, because IZs exhibit postrepolarization refractoriness, the difference in the effective refractory period (ERP), calculated using a propagation model of a single fiber of 100 cells, was 43 ms (156 ms in NZ and 199 ms in IZ). Either an increase in L-type Ca 2ϩ current (to simulate the effects of BAY Y5959) or a decrease of both or either delayed rectifier currents (e.g., to simulate the effects of azimilide, sotalol, and chromanol) had significant effects on NZ ERP. In contrast, the effects of these agents in IZs were minor, in agreement with measurements in the in situ canine infarcted heart. Therefore 1) because IZs exhibit postrepolarization refractoriness, conclusions drawn from APD measurements cannot be extrapolated directly to ERPs; 2) ionic currents that are the major determinants of APD and the ERP in NZs are less important in IZs; and 3) differential effects of either BAY Y5959 or azimilide in NZs versus IZs are predicted to decrease ERP dispersion and in so doing prevent initiation of arrhythmias in a substrate of inhomogeneous APD/ERPs. computer model; infarction; postrepolarization refractoriness; antiarrhythmic drugs SUSTAINED VENTRICULAR TACHYCARDIA (VT) can be induced by electrical stimulation in the canine heart 4-5 days after ligation of the left anterior descending coronary artery, during infarct healing. Reentrant circuits causing VT are located in a thin layer of epicardial cells that survive the infarct, the epicardial border zone (EBZ) (7). Action potential measurements on multicellular preparations isolated from the EBZ showed electrical (14, 31) and structural abnormalities (31).Action potential duration (APD) is similar in EBZ and normal myocardium, but EBZ myocardium has a longer effective refractory period (ERP) as a result of postrepolarization refractoriness (14,17,31). During acute myocardial ischemia, the ionic mechanism of postrepolarization refractoriness is thought to be due to delayed recovery of the sodium channel, which results from an elevated extracellularHowever, during the healing ...

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“…72 A rat experimental model of MI showed that downregulation of potassium channel gene expression (ERG, KCNE1, KCNQ1) and the potassium currents (IKr, IKs) occurs in surviving myocytes from the infarct zone 2 days after MI. 73 This suggests that major repolarizing currents (ie, IKr and IKs) may be reduced in the actual setting of the subacute phase of ACS in humans. Therefore, it is conceivable that patients with genetic variants, such as KCNQ1 G643S and KCNH2 K897T, would be at higher risk of TdP in the presence of additional reduction of repolarizing currents during the subacute phase of ACS.…”

Section: Discussionmentioning

confidence: 99%

Unveiling Specific Triggers and Precipitating Factors for Fatal Cardiac Events in Inherited Arrhythmia Syndromes

Nakajima

Kaneko

Kurabayashi

2015

Circ J

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Delayed rectifier K currents have reduced amplitudes and altered kinetics in myocytes from infarcted canine ventricle

Cited by 94 publications

References 22 publications

Optogenetic defibrillation terminates ventricular arrhythmia in mouse hearts and human simulations

Optogenetic defibrillation terminates ventricular arrhythmia in mouse hearts and human simulations

Electrical remodeling of the epicardial border zone in the canine infarcted heart: a computational analysis

Unveiling Specific Triggers and Precipitating Factors for Fatal Cardiac Events in Inherited Arrhythmia Syndromes

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