The Ultrarapid and the Transient Outward K+Current in Human Atrial Fibrillation. Their Possible Role in Postoperative Atrial Fibrillation

Brandt, Mathias C.; Priebe, Leo; Bohle, Thomas; Südkamp, Michael; Beuckelmann, Dirk J.

doi:10.1006/jmcc.2000.1221

Cited by 78 publications

(52 citation statements)

References 31 publications

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“…In some cases, more significant rate adaptation can be observed at the shortest CLs (Kim et al, 2002;Dobrev and Ravens, 2003). Similar alterations to those given by Courtemanche et al (1999) have been observed in other experiments as well (Dobrev and Ravens, 2003), including substantial reductions in I Ca,L (Bosch et al, 1999;Van Wagoner et al, 1999;Skasa et al, 2001;Workman et al, 2001) and I to (Van Wagoner et al, 1997;Bosch et al, 1999;Brandt et al, 2000;Grammer et al, 2000;Workman et al, 2001). The reduction in I Kur proposed by Courtemanche et al (1999) has been found in some studies (Van Wagoner et al, 1997;Brandt et al, 2000) but not in others (Grammer et al, 2000;Workman et al, 2001).…”

Section: Atrial Fibrillation-induced Changes In Rate Dependence and Msupporting

confidence: 83%

Dynamics of human atrial cell models: Restitution, memory, and intracellular calcium dynamics in single cells

Cherry

Hastings

Evans

2008

Progress in Biophysics and Molecular Biology

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Mathematical models of cardiac cells have become important tools for investigating the electrophysiological properties and behavior of the heart. As the number of published models increases, it becomes more difficult to choose a model appropriate for the conditions to be studied, especially when multiple models describing the species and region of the heart of interest are available. In this paper, we will review and compare two detailed ionic models of human atrial myocytes, the Nygren et al. model (NM) and the Courtemanche et al. model (CM). Although both models include the same transmembrane currents and are largely based on the same experimental data from human atrial cells, the two models exhibit vastly different properties, especially in their dynamical behavior, including restitution and memory effects. The CM produces pronounced rate adaptation of action potential duration (APD) with limited memory effects, while the NM exhibits strong rate dependence of resting membrane potential (RMP), limited APD restitution, and stronger memory, as well as delayed afterdepolarizations and auto-oscillatory behavior upon cessation of rapid pacing. Channel conductance modifications based on experimentally measured changes during atrial fibrillation modify rate adaptation and memory in both models, but do not change the primary rate-dependent properties of APD and RMP for the CM and NM, respectively. Two sets of proposed changes to the NM that yield a spike-and-dome action potential morphology qualitatively similar to the CM at slow pacing rates similarly do not change the underlying dynamics of the model. Moreover, interchanging the formulations of all transmembrane currents between the two models while leaving calcium handling and ionic concentrations intact indicates that the currents strongly influence memory and the rate adaptation of RMP, while intracellular calcium dynamics primarily determine APD rate adaptation. Our results suggest that differences in intracellular calcium handling between the two human atrial myocyte models are responsible for marked dynamical differences and may prevent reconciliation between the models by straightforward channel conductance modifications.

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Section: Atrial Fibrillation-induced Changes In Rate Dependence and Msupporting

confidence: 83%

Dynamics of human atrial cell models: Restitution, memory, and intracellular calcium dynamics in single cells

Cherry

Hastings

Evans

2008

Progress in Biophysics and Molecular Biology

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“…In contrast, I sus density did not differ among the three groups, similar to the findings of Yue et al (18). In human AF, some groups reported no changes in I sus in AF (3,15), whereas others have shown a reduction in I sus (12,2).…”

Section: Discussionsupporting

confidence: 87%

Chronic atrial fibrillation does not further decrease outward currents. It increases them.

Dun

Chandra

Danilo

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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“…In atrial myocytes from patients with valvular disease and persistent AF, we observed that the sustained K ϩ current was reduced by Ϸ50%, and there was a parallel reduction in the expression of Kv1.5 protein. 15 A similar conclusion was reached by Brandt et al 31 Although the Kv1.5 protein and functional K ϩ currents are reduced in AF, this does not imply that drugs that suppress this current would not be effective in prolonging atrial refractoriness, because there is typically an even greater reduction (60% to 70%) in the density of the L-type Ca 2ϩ current. 19 Thus, it is possible that drugs that suppress Kv1.5 currents might be more, rather than less, effective in AF patients than in controls.…”

Section: Discussionmentioning

confidence: 64%

Kv1.5 Is an Important Component of Repolarizing K ⁺ Current in Canine Atrial Myocytes

Fedida

Eldstrom

Hesketh

et al. 2003

Circulation Research

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Abstract-Although the canine atrium has proven useful in several experimental models of atrial fibrillation and for studying the effects of rapid atrial pacing on atrial electrical remodeling, it may not fully represent the human condition because of reported differences in functional ionic currents and ion channel subunit expression. In this study, we reassessed the molecular components underlying one current, the ultrarapid delayed rectifier current in canine atrium [I Kur(d) ], by evaluating the mRNA, protein, immunofluorescence, and currents of the candidate channels. Using reverse transcriptase-polymerase chain reaction, we found that Kv1.5 mRNA was expressed in canine atrium whereas message for Kv3.1 was not detected. Western analysis on cytosolic and membrane fractions of canine tissues, using selective antibodies, showed that Kv3.1 was only detectable in the brain preparations, whereas Kv1.5 was expressed at high levels in both atrial and ventricular membrane fractions. Confocal imaging performed on isolated canine atrial myocytes clearly demonstrated the presence of Kv1.5 immunostaining, whereas that of Kv3.1 was equivocal. Voltage-and current-clamp studies showed that 0.5 mmol/L tetraethylammonium had variable effects on sustained K ϩ currents, whereas a compound with demonstrated selectivity for hKv1.5 versus Kv3.1, hERG or the sodium channel, fully suppressed canine atrial I Kur tail currents and depressed sustained outward K ϩ current. This agent also increased action potential plateau potentials and action potential duration at 20% and 50% repolarization. These results suggest that in canine atria, as in other species including human, Kv1.5 protein is highly expressed and contributes to I Kur .

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The Ultrarapid and the Transient Outward K+Current in Human Atrial Fibrillation. Their Possible Role in Postoperative Atrial Fibrillation

Cited by 78 publications

References 31 publications

Dynamics of human atrial cell models: Restitution, memory, and intracellular calcium dynamics in single cells

Dynamics of human atrial cell models: Restitution, memory, and intracellular calcium dynamics in single cells

Chronic atrial fibrillation does not further decrease outward currents. It increases them.

Kv1.5 Is an Important Component of Repolarizing K ⁺ Current in Canine Atrial Myocytes

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The Ultrarapid and the Transient Outward K+Current in Human Atrial Fibrillation. Their Possible Role in Postoperative Atrial Fibrillation

Cited by 78 publications

References 31 publications

Dynamics of human atrial cell models: Restitution, memory, and intracellular calcium dynamics in single cells

Dynamics of human atrial cell models: Restitution, memory, and intracellular calcium dynamics in single cells

Chronic atrial fibrillation does not further decrease outward currents. It increases them.

Kv1.5 Is an Important Component of Repolarizing K + Current in Canine Atrial Myocytes

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Kv1.5 Is an Important Component of Repolarizing K ⁺ Current in Canine Atrial Myocytes