Electrophysiological features of the mouse sinoatrial node in relation to connexin distribution

Verheijck, E. E.; Kempen, M J van; Veereschild, M; Lurvink, J; Jongsma, Habo J.; Bouman, L. N.

doi:10.1016/s0008-6363(01)00364-9

Cited by 158 publications

(155 citation statements)

References 28 publications

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“…It has been shown in an immunohistochemical study that the mouse sinoatrial node pacemaking cells are negative for Cx40 and Cx43 but positive for Cx45, unlike surrounding atrial cells (Cx40/43 positive; Cx45 negative). 11 In the serial sections of kl Ϫgeo mice, X-gal-positive cells were restricted in a region negative for Cx40 ( Figure 6). This indicates specific expression of klotho in the sinoatrial node.…”

Section: Klotho Expression In Micementioning

confidence: 96%

Sinoatrial Node Dysfunction and Early Unexpected Death of Mice With a Defect of klotho Gene Expression

Takeshita¹,

Fujimori²,

Kurotaki³

et al. 2004

Circulation

196

144

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Background-Homozygous mutant mice with a defect of klotho gene expression (kl/kl) show multiple age-related disorders and premature death from unknown causes. Methods and Results-The kl/kl mice subjected to 20-hour restraint stress showed a high rate (20/30) of sudden death, which was associated with sinoatrial node dysfunction (conduction block or arrest). Heart rate and plasma norepinephrine of kl/kl mice, unlike those of wild-type (WT) mice, failed to increase during the stress. Intrinsic heart rate after pharmacological blockade of autonomic nerves in kl/kl mice was significantly lower than that in WT mice (380Ϯ33 versus 470Ϯ44 bpm; nϭ7). The sinus node recovery time after an overdrive pacing (600 bpm, 30 seconds) in kl/kl mice was significantly longer than in WT mice (392Ϯ37 versus 233Ϯ24 ms; nϭ6). In isolated sinoatrial node preparations, the positive chronotropic effect of isoproterenol was significantly less, whereas the negative chronotropic effect of acetylcholine was significantly greater in kl/kl than in WT mice. There was no degenerative structural change in the sinoatrial node of kl/kl mice. The precise localization of klotho was analyzed in newly prepared klotho-null mice with a reporter gene system (kl Ϫgeo ). Homozygous kl Ϫgeo mice showed characteristic age-associated phenotypes that were almost identical to those of kl/kl mice. In the kl Ϫgeo mice, klotho expression was recognized exclusively in the sinoatrial node region in the heart in addition to parathyroid, kidney, and choroid plexus. Conclusions-In the heart, klotho is expressed solely at the sinoatrial node. klotho gene expression is essential for the sinoatrial node to function as a dependable pacemaker under conditions of stress.

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Section: Klotho Expression In Micementioning

confidence: 96%

Sinoatrial Node Dysfunction and Early Unexpected Death of Mice With a Defect of klotho Gene Expression

Takeshita¹,

Fujimori²,

Kurotaki³

et al. 2004

Circulation

196

144

View full text Add to dashboard Cite

show abstract

“…Cx40 is mainly expressed in the atrium and in the conduction system [44][45][46][47][48][49], while Cx43 can be found both in atrial and ventricular cells but not in sinoatrial and atrioventricular nodes [46,[48][49][50][51][52][53][54][55]. Cx45 is preferentially expressed in sinoatrial and atrioventricular nodes, His-bundle and bundle branches [56][57][58]. More recently, Cx30.2 expression was described in mouse sinus node and in the conduction system, but the human ortholog Cx31.9 is not expressed in the human heart [59][60][61].…”

Section: The Distribution Of Gap Junctionsmentioning

confidence: 99%

Role of Gap Junction Channel in the Development of Beat-to-Beat Action Potential Repolarization Variability and Arrhythmias

Magyar

Bányász

Szentandrássy

et al. 2014

CPD

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The short-term beat-to-beat variability of cardiac action potential duration (SBVR) occurs as a random alteration of the ventricular repolarization duration. SBVR has been suggested to be more predictive of the development of lethal arrhythmias than the action potential prolongation or QT prolongation of ECG alone. The mechanism underlying SBVR is not completely understood but it is known that SBVR depends on stochastic ion channel gating, intracellular calcium handling and intercellular coupling.Coupling of single cardiomyocytes significantly decreases the beat-to-beat changes in action potential duration (APD) due to the electrotonic current flow between neighboring cells. The magnitude of this electrotonic current depends on the intercellular gap junction resistance. Reduced gap junction resistance causes greater electrotonic current flow between cells, and reduces SBVR.Myocardial ischaemia (MI) is known to affect gap junction channel protein expression and function. MI increases gap junction resistance that leads to slow conduction, APD and refractory period dispersion, and an increase in SBVR. Ultimately, development of reentry arrhythmias and fibrillation are associated post-MI. Antiarrhythmic drugs have proarrhythmic side effects requiring alternative approaches. A novel idea is to target gap junction channels. Specifically, the use of gap junction channel enhancers and inhibitors may help to reveal the precise role of gap junctions in the development of arrhythmias. Since cell-to-cell coupling is represented in SBVR, this parameter can be used to monitor the degree of coupling of myocardium.

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“…These channels form a low-resistance pathway between adjacent myocytes and consist of connexin proteins. The connexin family is a large multigene family, and the channels formed by different members of this family have distinct electrical and regulatory properties (Reisner et al, 2009;Gros & Jongsma, 1996;Verheijck et al, 2001;Valiunas et al, 2002). Voltage sensitivity is particularly important in regulating the intercellular coupling between excitable cells.…”

Section: Cardiac Electrical Properties Of Connexins and The Methods Fmentioning

confidence: 99%

The Remodeling of Connexins Localized at Pulmonary Vein – Left Atria in Triggering and Maintenance of Atrial Fibrillation

Zhong¹,

Xiong²,

Song³

et al. 2012

Advances in Electrocardiograms - Clinical Applications

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Electrophysiological features of the mouse sinoatrial node in relation to connexin distribution

Cited by 158 publications

References 28 publications

Sinoatrial Node Dysfunction and Early Unexpected Death of Mice With a Defect of klotho Gene Expression

Sinoatrial Node Dysfunction and Early Unexpected Death of Mice With a Defect of klotho Gene Expression

Role of Gap Junction Channel in the Development of Beat-to-Beat Action Potential Repolarization Variability and Arrhythmias

The Remodeling of Connexins Localized at Pulmonary Vein – Left Atria in Triggering and Maintenance of Atrial Fibrillation

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