Action Potential Prolongation and Potassium Currents in Left-Ventricular Myocytes Isolated from Hypertrophied Rabbit Hearts

McIntosh, M.A.; Cobbe, SM; Kane, Kathleen A.; Rankin, Andrew C.

doi:10.1006/jmcc.1997.0570

Cited by 57 publications

(40 citation statements)

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“…In our study, transmural heterogeneities in ionic currents have been incorporated based on rabbit experimental data (McIntosh et al, 1998(McIntosh et al, , 2000Xu et al, 2001), as done in a previous simulation study (Saucerman et al, 2004). Consistent with previous research (McIntosh et al, 1998(McIntosh et al, , 2000Viswanathan et al, 1999;Xu et al, 2001;Gima and Rudy, 2002;Idriss and Wolf, 2004;Saucerman et al, 2004;Sampson and Henriquez, 2005), our study shows that the transmural differences in ionic currents result in differences in the shape and duration of the action potential in epicardial, midmyocardial and endocardial cells. In isolated single cells, the presence of a prominent I to current in epicardial and midmycardial myocytes gives rise to a notch following the upstroke of the action potential, which is absent in endocardial action potentials (Fig.…”

Section: Transmural Electrophysiological Heterogeneities In the Ventrsupporting

confidence: 77%

Section: Transmural Electrophysiological Heterogeneities In the Ventrmentioning

confidence: 99%

“…Experimental studies using isolated endocardial, midmyocardial and epicardial myocytes report transmural differences in I to in canine, rabbit, guinea pig and human (Li et al, 1998;McIntosh et al, 1998;Antzelevitch et al, 1999a, b), in I Na in canine (Antzelevitch et al, 1999a, b), in I Ks in canine and rabbit (Liu and Antzelevitch, 1995;Xu et al, 2001;Yan et al, 2001), and to a smaller extent, in I Kr in rabbit ). In our study, transmural heterogeneities in ionic currents have been incorporated based on rabbit experimental data (McIntosh et al, 1998(McIntosh et al, , 2000Xu et al, 2001), as done in a previous simulation study (Saucerman et al, 2004). Consistent with previous research (McIntosh et al, 1998(McIntosh et al, , 2000Viswanathan et al, 1999;Xu et al, 2001;Gima and Rudy, 2002;Idriss and Wolf, 2004;Saucerman et al, 2004;Sampson and Henriquez, 2005), our study shows that the transmural differences in ionic currents result in differences in the shape and duration of the action potential in epicardial, midmyocardial and endocardial cells.…”

Section: Transmural Electrophysiological Heterogeneities In the Ventrmentioning

confidence: 99%

“…Transmural ventricular heterogeneities in the transient outward potassium current (I to ), in the slow and rapid delayed rectifier potassium currents (I Ks , I Kr ), and in the sodium (I Na ) current were incorporated in the model based on experimental data (McIntosh et al, 1998(McIntosh et al, , 2000Dumaine et al, 1999;, as done previously (Saucerman et al, 2004). The above are the main currents responsible for transmural heterogeneities in action potential shape and duration.…”

Section: Computational Modelmentioning

confidence: 99%

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The role of transmural ventricular heterogeneities in cardiac vulnerability to electric shocks

Maharaj

Blake

Trayanova

et al. 2008

Progress in Biophysics and Molecular Biology

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Transmural electrophysiological heterogeneities have been shown to contribute to arrhythmia induction in the heart; however, their role in defibrillation failure has never been examined. The goal of this study is to investigate how transmural heterogeneities in ionic currents and gap-junctional coupling contribute to arrhythmia generation following defibrillation strength shocks. This study used a 3D anatomically realistic bidomain model of the rabbit ventricles. Transmural heterogeneity in ionic currents and reduced sub-epicardial intercellular coupling were incorporated based on experimental data. The ventricles were paced apically, and truncated-exponential monophasic shocks of varying strength and timing were applied via large external electrodes. Simulations demonstrate that inclusion of transmural heterogeneity in ionic currents results in an increase in vulnerability to shocks, reflected in the increased upper limit of vulnerability, ULV, and the enlarged vulnerable window, VW. These changes in vulnerability stem from increased post-shock dispersion in repolarisation as it increases the likelihood of establishment of re-entrant circuits. In contrast, reduced sub-epicardial coupling results in decrease in both ULV and VW. This decrease is caused by altered virtual electrode polarisation around the region of sub-epicardal uncoupling, and specifically, by the increase in (1) the amount of positively polarised myocardium at shock-end and (2) the spatial extent of post-shock wavefronts.

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Section: Transmural Electrophysiological Heterogeneities In the Ventrsupporting

confidence: 77%

Section: Transmural Electrophysiological Heterogeneities In the Ventrmentioning

confidence: 99%

Section: Transmural Electrophysiological Heterogeneities In the Ventrmentioning

confidence: 99%

Section: Computational Modelmentioning

confidence: 99%

See 2 more Smart Citations

The role of transmural ventricular heterogeneities in cardiac vulnerability to electric shocks

Maharaj

Blake

Trayanova

et al. 2008

Progress in Biophysics and Molecular Biology

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“…However, their effects on the regulation of the electrical activity of the heart are not yet well studied, specifically in terms of the role of potassium channels (namely, I K and I K1 ) during eccentric cardiac hypertrophy. Its importance stems from the fact that cardiac hypertrophy is characterized by a prolongation of the action potential duration, an almost universal finding in ventricular cells exposed to chronic workload leading to cardiac hypertrophy (33,34,36,60). Alterations in the activity of the potassium channels have direct effects on the action potential duration and configuration, which are important determinants of myocardial contraction (33,34).…”

mentioning

confidence: 99%

Basal and IGF-I-dependent regulation of potassium channels by MAP kinases and PI3-kinase during eccentric cardiac hypertrophy

Teos¹,

Zhao²,

Alvin³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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The potassium channels IK and IK1, responsible for the action potential repolarization and resting potential respectively, are altered during cardiac hypertrophy. The activation of insulin-like growth factor-I (IGF-I) during hypertrophy may affect channel activity. The aim was to examine the modulatory effects of IGF-I on IK and IK1 through mitogenactivated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways during hypertrophy. With the use of specific inhibitors for ERK1/2 (PD98059), p38 MAPK (SB203580) and PI3K/Akt (LY294002), Western blot and whole cell patch-clamp were conducted on sham and aorto-caval shunt-induced hypertrophy adult rat myocytes. Basal activation levels of MAPKs and Akt were increased during hypertrophy. Acute IGF-I (10 Ϫ8 M) enhanced basal activation levels of these kinases in normal hearts but only those of Akt in hypertrophied ones. IK and IK1 activities were lowered by IGF-I. Inhibition of ERK1/2, p38 MAPK, or Akt reduced basal IK activity by 70, 32, or 50%, respectively, in normal cardiomyocytes vs. 53, 34, or 52% in hypertrophied ones. However, basal activity of IK1 was reduced by 45, 48, or 45% in the former vs. 63, 43, or 24% in the latter. The inhibition of either MAPKs or Akt alleviated IGF-I effects on IK and IK1. We conclude that basal IK and IK1 are positively maintained by steady-state Akt and ERK activities.

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Ion Channels and Cardiac Arrhythmia in Heart Disease

Makielski

Fozzard

2002

Comprehensive Physiology

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Action Potential Prolongation and Potassium Currents in Left-Ventricular Myocytes Isolated from Hypertrophied Rabbit Hearts

Cited by 57 publications

References 0 publications

The role of transmural ventricular heterogeneities in cardiac vulnerability to electric shocks

The role of transmural ventricular heterogeneities in cardiac vulnerability to electric shocks

Basal and IGF-I-dependent regulation of potassium channels by MAP kinases and PI3-kinase during eccentric cardiac hypertrophy

Ion Channels and Cardiac Arrhythmia in Heart Disease

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