Electrical Activity of the Mouse Pulmonary Vein Myocardium

Tsuneoka, Yousuke; Kobayashi, Yuka; Honda, Yoriko; Namekata, Iyuki; Tanaka, Hikaru

doi:10.1254/jphs.12062sc

Cited by 26 publications

(28 citation statements)

References 18 publications

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“…[25][26][27][28] Coverslips with cells were placed in a chamber on the stage of the inverted microscope and perfused with HEPES-Tyrode solution of the following composition (mM): NaCl 143, KCl 5.4, MgCl 2 1.8, CaCl 2 2, NaH 2 PO 4 0.33, glucose 5.5 and HEPES 20. The solution was gassed with 100% O 2 .…”

Section: )mentioning

confidence: 99%

Effect of Terfenadine and Pentamidine on the hERG Channel and Its Intracellular Trafficking: Combined Analysis with Automated Voltage Clamp and Confocal Microscopy

Tanaka

Takahashi

Hamaguchi

et al. 2014

Biological & Pharmaceutical Bulletin

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The effects of terfenadine and pentamidine on the human ether-a-go-go related gene (hERG) channel current and its intracellular trafficking were evaluated. Green fluorescent protein (GFP)-linked hERG channels were expressed in HEK293 cells, and the membrane current was measured by an automated whole cell voltage clamp system. To evaluate drug effects on channel trafficking to the cell membrane, the fraction of channel present on the cell membrane was quantified by current measurement after drug washout and confocal microscopy. Terfenadine directly blocked the hERG channel current but had no effect on trafficking of hERG channels to the cell membrane after application in culture medium for 2 d. In contrast, pentamidine had no direct effect on the hERG channel current but reduced trafficking of hERG channels. The two drugs inhibited hERG channel function through different mechanisms: terfenadine through direct channel blockade and pentamidine through inhibition of channel trafficking to the cell membrane. Combined use of automated voltage clamp and confocal microscopic analyses would provide insights into the mechanisms of drug-induced QT-prolongation and arrhythmogenesis.

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Section: )mentioning

confidence: 99%

Effect of Terfenadine and Pentamidine on the hERG Channel and Its Intracellular Trafficking: Combined Analysis with Automated Voltage Clamp and Confocal Microscopy

Tanaka

Takahashi

Hamaguchi

et al. 2014

Biological & Pharmaceutical Bulletin

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“…Pharmacological analyses revealed that hyperpolarization and depolarization were mediated by β-and α-adrenergic receptors, respectively, and that simultaneous activation of both receptor types are necessary for the generation of automatic activity. 22,26,39) In case of the mouse pulmonary vein myocardium, 23) application of noradrenaline to quiescent preparations induced automatic activity (Fig. 1C), which were often preceded by hyperpolarization or depolarization of the resting membrane potential.…”

Section: 21)mentioning

confidence: 94%

“…23) Automatic activity was observed in about half of the preparations, which appeared in three different waveform types. The first was a constant firing which was similar to those observed in the guinea pig, and the second was a repetitive burst with a similar maximum diastolic potential during and between bursts resembling the waveform observed in the rat.…”

Section: )mentioning

confidence: 99%

“…Inhibition of the pathways to provide Ca 2+ to the pulmonary vein cardiomyocytes, such as the stretch activated channels, may inhibit pulmonary vein electrical activity through reduction of intracellular Ca 2+ load. Increasing the repolarization power of pulmonary vein cardiomyocytes might be effective in suppressing their automaticity 23,33,37) ; this should be achieved without shortening the refractory period of the working myocardium. Modifying the effect of various neurohumoral factors may also be effective.…”

Section: Pharmacological Strategies Against Pulmonary Vein Automaticitymentioning

confidence: 99%

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Electrophysiological and Pharmacological Properties of the Pulmonary Vein Myocardium

Namekata

Tsuneoka

Tanaka

2013

Biological & Pharmaceutical Bulletin

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The pulmonary vein contains a myocardial layer extending from the left atrium, which is receiving attention as the source of ectopic electrical activity underlying atrial fibrillation. Electrophysiological and pharmacological analysis of the pulmonary vein myocardium performed in various experimental animal species have revealed characteristics such as presence of intracellular Ca 2+ oscillations and low repolarizing potency. The automaticity of the pulmonary vein myocardium is affected by various neurotransmitters, hormones and pharmacological agents. Clarification of the mechanisms and regulation of pulmonary vein automaticity would lead to the development of novel therapeutic strategies and pharmacological agents for atrial fibrillation.

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“…In humans, the normal resting cardiac rhythm is ∼1 Hz, but during AF the atrial chambers can display activity in excess of 5 Hz due to aberrant electrical signals [6]. It is well established that a population of distinct myocyte-like cells, called pulmonary vein sleeve cells (PVCs), which surround the pulmonary veins, cause AF by autonomously generating action potentials (APs) that propagate into the left atrial chamber [7,8].…”

Section: Pulmonary Vein Sleeve Cells Trigger Atrial Fibrillationmentioning

confidence: 99%

Pulmonary vein sleeve cell excitation–contraction-coupling becomes dysynchronized by spontaneous calcium transients

Rietdorf

Masoud

McDonald

et al. 2015

Biochemical Society Transactions

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Atrial fibrillation (AF) is the most common form of sustained cardiac arrhythmia. Substantial evidence indicates that cardiomyocytes located in the pulmonary veins [pulmonary vein sleeve cells (PVCs)] cause AF by generating ectopic electrical activity. Electrical ablation, isolating PVCs from their left atrial junctions, is a major treatment for AF. In small rodents, the sleeve of PVCs extends deep inside the lungs and is present in lung slices. Here we present data, using the lung slice preparation, characterizing how spontaneous Ca2+ transients in PVCs affect their capability to respond to electrical pacing. Immediately after a spontaneous Ca2+ transient the cell is in a refractory period and it cannot respond to electrical stimulation. Consequently, we observe that the higher the level of spontaneous activity in an individual PVC, the less likely it is that this PVC responds to electrical field stimulation. The spontaneous activity of neighbouring PVCs can be different from each other. Heterogeneity in the Ca2+ signalling of cells and in their responsiveness to electrical stimuli are known pro-arrhythmic events. The tendency of PVCs to show spontaneous Ca2+ transients and spontaneous action potentials (APs) underlies their potential to cause AF.

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Electrical Activity of the Mouse Pulmonary Vein Myocardium

Cited by 26 publications

References 18 publications

Effect of Terfenadine and Pentamidine on the hERG Channel and Its Intracellular Trafficking: Combined Analysis with Automated Voltage Clamp and Confocal Microscopy

Effect of Terfenadine and Pentamidine on the hERG Channel and Its Intracellular Trafficking: Combined Analysis with Automated Voltage Clamp and Confocal Microscopy

Electrophysiological and Pharmacological Properties of the Pulmonary Vein Myocardium

Pulmonary vein sleeve cell excitation–contraction-coupling becomes dysynchronized by spontaneous calcium transients

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