Calcium Currents in Diseased Human Cardiac Cells

Ouadid, H.; Albat, Bernard; Nargeot, Joël

doi:10.1097/00005344-199502000-00014

Cited by 123 publications

(66 citation statements)

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“…In the early stages of heart failure marked by hypertrophy, I Ca-L may be increased (31, 37), whereas in the failing heart it may be unchanged (27, 112) or decreased (97,166,182). Studies of I Ca-L density in human heart failure suggest that current density is held near normal levels by increased phosphorylation, despite the fact that the response to ␤-adrenergic receptor-mediated phosphorylation is attenuated (39,153). In that regard, single channel studies in failing myocytes suggest that phosphorylation may offset a reduction in channel number by increasing open channel probability (193).…”

Section: Role Of Cardiac Dynamics In the Generation Of Ventricular Armentioning

confidence: 99%

Mechanisms of ventricular arrhythmias: a dynamical systems-based perspective

Cherry

Fenton

Gilmour

2012

American Journal of Physiology-Heart and Circulatory Physiology

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Cherry EM, Fenton FH, Gilmour RF Jr. Mechanisms of ventricular arrhythmias: a dynamical systems-based perspective. Am J Physiol Heart Circ Physiol 302: H2451-H2463, 2012. First published March 30, 2012 doi:10.1152/ajpheart.00770.2011Defining the cellular electrophysiological mechanisms for ventricular tachyarrhythmias is difficult, given the wide array of potential mechanisms, ranging from abnormal automaticity to various types of reentry and kk activity. The degree of difficulty is increased further by the fact that any particular mechanism may be influenced by the evolving ionic and anatomic environments associated with many forms of heart disease. Consequently, static measures of a single electrophysiological characteristic are unlikely to be useful in establishing mechanisms. Rather, the dynamics of the electrophysiological triggers and substrates that predispose to arrhythmia development need to be considered. Moreover, the dynamics need to be considered in the context of a system, one that displays certain predictable behaviors, but also one that may contain seemingly stochastic elements. It also is essential to recognize that even the predictable behaviors of this complex nonlinear system are subject to small changes in the state of the system at any given time. Here we briefly review some of the short-, medium-, and long-term alterations of the electrophysiological substrate that accompany myocardial disease and their potential impact on the initiation and maintenance of ventricular arrhythmias. We also provide examples of cases in which small changes in the electrophysiological substrate can result in rather large differences in arrhythmia outcome. These results suggest that an interrogation of cardiac electrical dynamics is required to provide a meaningful assessment of the immediate risk for arrhythmia development and for evaluating the effects of putative antiarrhythmic interventions.alternans; dynamics; spiral waves; ventricle THIS REVIEW ARTICLE is part of a collection on Electrophysiology and Excitation-Contraction Coupling. Other articles appearing in this collection, as well as a full archive of all Review collections, can be found online at http://ajpheart. physiology.org/.

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Section: Role Of Cardiac Dynamics In the Generation Of Ventricular Armentioning

confidence: 99%

Mechanisms of ventricular arrhythmias: a dynamical systems-based perspective

Cherry

Fenton

Gilmour

2012

American Journal of Physiology-Heart and Circulatory Physiology

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“…Alterations in atrial cellular electrophysiology have been reported in patients [2][3][4][5][6] and experimental animals 7,[15][16][17] with atrial disease and/or dilation. Similar to our observations at slower rates, APD was not substantially altered in dogs with tricuspid insufficiency 15 and chronic mitral regurgitation.…”

Section: Comparison With Previous Studies Of Cellular Electrophysiolomentioning

confidence: 99%

“…Atrial myocytes from hearts with terminal failure showed decreased L-type Ca 2ϩ current (I Ca ) compared with relatively normal hearts. 3 Koumi et al 4 noted reduced atrial inward rectifier current (I K1 ) in patients with CHF; however, Le Grand et al 5 found no change in I K1 in dilated human atria, whereas I Ca and transient outward K ϩ current (I to ) were reduced. These data are limited by a wide range of heart diseases and variable drug therapy.…”

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confidence: 99%

Effects of Experimental Heart Failure on Atrial Cellular and Ionic Electrophysiology

et al. 2000

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Background-Congestive heart failure (CHF) is frequently associated with atrial fibrillation (AF), but little is known about the effects of CHF on atrial cellular electrophysiology. Methods and Results-We studied action potential (AP) properties and ionic currents in atrial myocytes from dogs with CHF induced by ventricular pacing at 220 to 240 bpm for 5 weeks. Atrial myocytes from CHF dogs were hypertrophied (meanϮSEM capacitance, 89Ϯ2 pF versus 71Ϯ2 pF in control, nϭ160 cells per group, PϽ0.001). CHF significantly reduced the density of L-type Ca 2ϩ current (I Ca ) by Ϸ30%, of transient outward K ϩ current (I to ) by Ϸ50%, and of slow delayed rectifier current (I Ks ) by Ϸ30% without altering their voltage dependencies or kinetics. The inward rectifier, ultrarapid and rapid delayed rectifier, and T-type Ca 2ϩ currents were not altered by CHF. CHF increased transient inward Na ϩ /Ca 2ϩ exchanger (NCX) current by Ϸ45%. The AP duration of atrial myocytes was not altered by CHF at slow rates but was increased at faster rates, paralleling in vivo refractory changes. CHF created a substrate for AF, prolonging mean AF duration from 8Ϯ4 to 535Ϯ82 seconds (PϽ0.01). Conclusions-Experimental CHF selectively decreases atrial I to , I Ca , and I Ks , increases NCX current, and leaves other currents unchanged. The cellular electrophysiological remodeling caused by CHF is quite distinct from that caused by atrial tachycardia, highlighting important differences in the cellular milieu characterizing different clinically relevant AF

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“…Similar reduction of I to and I K1 has been observed in ventricular cells isolated from failing human hearts. 3,17 In terms of I Ca,L , various changes such as an increase, 18 no change, 19 and a decrease 20 in the density of I Ca,L have been reported in myocytes of failing human hearts. In BIO 14.6 hamsters, the density of I Ca,L was significantly depressed at the late heart failure stage, although it was unaltered at 20 weeks (unpublished observations).…”

Section: Matsumoto Et Al Et a Receptor Blockade On Electrical Remodelingmentioning

confidence: 99%

Long-Term Endothelin A Receptor Blockade Inhibits Electrical Remodeling in Cardiomyopathic Hamsters

Matsumoto

Aihara²,

Yamauchi-Kohno³

et al. 2002

Circulation

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Background-The endothelin (ET) system is activated in failing hearts. Congestive heart failure frequently is associated with ventricular arrhythmias, which may result from electrical remodeling such as changes of ionic current density and heterogeneous action potential prolongation. We examined the effects of long-term ET A receptor blockade on the electrophysiological properties of ventricular cells, the surface ECG, and the survival in BIO 14.6 cardiomyopathic hamsters. Methods and Results-Membrane currents and action potentials were recorded from left ventricular cells isolated from normal F1␤ hamsters and cardiomyopathic BIO 14.6 hamsters untreated and chronically treated with TA-0201, an ET A receptor antagonist. In ventricular cells of untreated BIO 14.6 hamsters, the action potential duration was prolonged and the densities of the L-type Ca 2ϩ current (I Ca,L ), the transient outward current (I to ), the delayed rectifier K ϩ current (I K ), and the inward rectifier K ϩ current (I K1 ) were decreased compared with those of F1␤ hamsters. Long-term treatment with the ET A receptor antagonist significantly attenuated action potential duration prolongation and reduction of I to , I K , and I Ca,L in BIO 14.6 ventricular cells. Long-term ET A receptor blockade prevented the QT prolongation and ventricular arrhythmias and improved the survival rate in the cardiomyopathic hamsters. Conclusions-Long-term treatment with an ET

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Calcium Currents in Diseased Human Cardiac Cells

Cited by 123 publications

References 0 publications

Mechanisms of ventricular arrhythmias: a dynamical systems-based perspective

Mechanisms of ventricular arrhythmias: a dynamical systems-based perspective

Effects of Experimental Heart Failure on Atrial Cellular and Ionic Electrophysiology

Long-Term Endothelin A Receptor Blockade Inhibits Electrical Remodeling in Cardiomyopathic Hamsters

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