Injury current modulates afterdepolarizations in single human ventricular cells

Verkerk, Arie O.; Veldkamp, Marieke W.; Jonge, N. De; Wilders, Ronald; Ginneken, A. C. G. Van

doi:10.1016/s0008-6363(00)00064-x

Cited by 32 publications

(33 citation statements)

References 30 publications

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“…3 Action potential shortening is an antiarrhythmic intervention for DAD-related arrhythmias. 4,11 In our study, the action potentials recorded from both rabbit and human myocytes were shortened by acute application of 3-PUFAs in both rabbit and human myocytes, except at fast (Ͼ2 Hz) stimulation rates ( Figure 3B). The shortening of the action potential by 3-PUFAs in human myocytes may have contributed to a reduced number of DADs.…”

Section: Fish Oil Shortens the Action Potential Durationssupporting

confidence: 49%

Acute Administration of Fish Oil Inhibits Triggered Activity in Isolated Myocytes From Rabbits and Patients With Heart Failure

et al. 2008

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Background-Fish oil reduces sudden death in patients with prior myocardial infarction. Sudden death in heart failure may be due to triggered activity based on disturbed calcium handling. We hypothesized that superfusion with 3-polyunsaturated fatty acids (3-PUFAs) from fish inhibits triggered activity in heart failure. Methods and Results-Ventricular myocytes were isolated from explanted hearts of rabbits with volume-and pressure-overload-induced heart failure and of patients with end-stage heart failure. Membrane potentials (patch-clamp technique) and intracellular calcium (indo-1 fluorescence) were recorded after 5 minutes of superfusion with Tyrode's solution (control), -9 monounsaturated fatty acid oleic acid (20 mol/L), or 3-PUFAs (docosahexaenoic acid or eicosapentaenoic acid 20 mol/L). 3-PUFAs shortened the action potential at low stimulation frequencies and caused an Ϸ25% decrease in diastolic and systolic calcium (all PϽ0.05). Subsequently, noradrenalin and rapid pacing were used to evoke triggered activity, delayed afterdepolarizations, and calcium aftertransients. 3-PUFAs abolished triggered activity and reduced the number of delayed afterdepolarizations and calcium aftertransients compared with control and oleic acid. 3-PUFAs reduced action potential shortening and intracellular calcium elevation in response to noradrenalin. Results from human myocytes were in accordance with the findings obtained in rabbit myocytes. Conclusion-Superfusion with 3-PUFAs from fish inhibits triggered arrhythmias in myocytes from rabbits and patients with heart failure by lowering intracellular calcium and reducing the response to noradrenalin. (Circulation. 2008;117: 536-544.)

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Section: Fish Oil Shortens the Action Potential Durationssupporting

confidence: 49%

Acute Administration of Fish Oil Inhibits Triggered Activity in Isolated Myocytes From Rabbits and Patients With Heart Failure

et al. 2008

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“…4). This effect is comparable to previous studies, where real cells showing EADs were coupled to a passive RC circuit [11][12][13][14]. In our experiments, however, we additionally demonstrated that this occurs under conditions of failing as well as successful action potential propagation (Fig.…”

Section: Discussionsupporting

confidence: 92%

Action potential transfer at the Purkinje-ventricular junction: role of transitional cells

Verkerk

Veldkamp²,

Ginneken³

et al.

2001 Conference Proceedings of the 23rd Annual International Conference of the IEEE Engineering in Medicine and Biology Society

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-At the Purkinje (P) -ventricular (V) junction a zone of "transitional (T)" cells is found. In the present study we investigated the role of these T cells in P-to-V conduction. Using the "model clamp" technique, an experimentally recorded rabbit P cell was coupled to a phase-2 Luo and Rudy (LR) model cell, which in turn was coupled to a strand of phase-2 LR model cells. In our experiments, the single LR model represents the T cell, while the strand of LR models represents subendocardial V cells. This approach enabled us to change selectively coupling conductance (G c ) between cells, presence of T cell, and relative size of cells. We demonstrated that: 1) a decrease of G c between P-T and T-V increases the delay of V activation, 2) the delay of V activation is importantly due to conduction between T and V cells, 3) there is a critical G c for successful conduction at the P-V junction, 4) the critical value of G c for conduction at the P-V junction is lower in presence (11.0±0.7 nS) than in absence (13.7±0.8 nS) of the T cell, and 5) enlargement of the T zone size hampers successful P-to-V conduction. Keywords -Heart, electrophysiology, gap junction, Purkinjeventricular junction, conduction I. INTRODUCTIONAt the junction between Purkinje (P) fibers and ventricular (V) myocardium a tiny zone is found populated with cells that are called "transitional (T)" [1,2]. The P fibers are connected via short thin branches to sheets of these T cells, which in turn are connected via short thin branches to the V myocardium [3]. This anatomic arrangement is thought to form a high-resistance barrier [3], which may benefit P-to-V conduction by shielding a relatively small P fiber from the electrical load imposed by a relatively large V mass [4]. In addition, it is thought to contribute to the discontinuous conduction at the P-V junction [4,5]. In the present study, we measured the effects of the presence of T cells on action potential transfer at the P-V junction. Using an extended version of the "model clamp" technique [6], we electrically coupled an isolated rabbit cardiac P cell by any desired value of "gap junctional conductance" to a strand of ventricular cells of the phase-2 Luo and Rudy (LR) model [7]. In between, we can add another LR model cell, representing in our experimental set-up the T cell. This approach allowed us to study selectively the importance of T cells in conduction at the P-V junction. II. METHODOLOGYCell preparation. Single P cells were isolated from rabbit hearts by enzymatic dissociation. Hearts were quickly removed from anaesthetized rabbits (1 ml/kg Hypnorm), mounted on a Langendorff perfusion apparatus, and perfused with the following solutions: 1) Tyrode's solution for 10 min; 2) nominally 'Ca 2+ -free' Tyrode's solution for 10 min; and 3) nominally 'Ca 2+ -free' Tyrode's solution with collagenase (59 U/L type B and 150 U/L type P; Boehringer) and 250 mg/L trypsin inhibitor (Boehringer) for 30 min. Subsequently, freerunning P fibers, free from ventricular tissue, were excised from both ven...

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“…Eventually, the corresponding command potential V cmd is amplified and injected into the myocyte. This method was used to study, among others, the impact of depolarized, inexcitable cardiomyocytes in the ischemic tissue on the neighbouring cells (the so-called injury current; Verkerk et al 2000), or consequences of artificially implemented specific ionic current in cells where it is not naturally present (e.g. transient outward potassium current I to in guinea-pig or canine endocardial ventricular myocytes - Dong et al 2006).…”

Section: Model Clampmentioning

confidence: 99%

Advances in patch clamp technique: towards higher quality and quantity

Bébarová¹

2012

gpb

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Abstract. The patch clamp technique, developed in late 1970s, started a new period of experimental cardiac electrophysiology enabling measurement of ionic currents on isolated cardiomyocytes down to the level of single channels. Since that time, the technique has been substantially improved by development of several upgraded modifications providing so far unavailable data (e.g. action potential clamp, dynamic clamp, high-resolution scanning patch clamp), or facilitating the patch clamp technique by increasing its efficiency (planar patch clamp, automated patch clamp). The current review summarizes the leading new patch clamp based techniques used in cardiac cellular electrophysiology, their principles and prominent related papers.

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Injury current modulates afterdepolarizations in single human ventricular cells

Cited by 32 publications

References 30 publications

Acute Administration of Fish Oil Inhibits Triggered Activity in Isolated Myocytes From Rabbits and Patients With Heart Failure

Acute Administration of Fish Oil Inhibits Triggered Activity in Isolated Myocytes From Rabbits and Patients With Heart Failure

Action potential transfer at the Purkinje-ventricular junction: role of transitional cells

Advances in patch clamp technique: towards higher quality and quantity

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