Gap junctional uncoupling plays a trigger role in the antiarrhythmic effect of ischaemic preconditioning

Papp, Rita; Gönczi, Márton; Kovács, Mária; Seprényi, György; Végh, Ágnes

doi:10.1016/j.cardiores.2007.02.021

Cited by 45 publications

(78 citation statements)

References 47 publications

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“…A number of papers support the contention that reduced function of gap junction channels often associate with ischaemia and arrhythmias [75,[94][95][96][97]. Therefore the modification of gap junction channel function can be a target of arrhythmia treatment.…”

Section: Gap Junction Enhancers and Inhibitorsmentioning

confidence: 95%

“…On the other hand reduced intercellular coupling can limit the spread of mediators of cell death and this way it may reduce the size of infarction [153]. Administration of gap junction channel inhibitors like carbenoxolone can partly close gap junctions, preventing these channels from further uncoupling during the prolonged ischaemia to provide antiarrhythmic protection similar to preconditioning [97]. Partial uncoupling of gap junctions prior to ischaemia by ischemic-preconditioning preserves the electrical coupling of cells during a subsequent ischemic insult, indicating that a partial closure of gap junctions may play a trigger role in the protection [94,96,154,155].…”

Section: The Possible Antiarrhythmic Effects Of Gap Junction Modulatorsmentioning

confidence: 99%

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Chemistry, Physiology, and Pharmacology of β.-Adrenergic Mechanisms in the Heart. Why are .β-Blocker Antiarrhythmics Superior?

Szentmiklósi¹,

Szentandrássy²,

Hegyi³

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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Section: Gap Junction Enhancers and Inhibitorsmentioning

confidence: 95%

Section: The Possible Antiarrhythmic Effects Of Gap Junction Modulatorsmentioning

confidence: 99%

Chemistry, Physiology, and Pharmacology of β.-Adrenergic Mechanisms in the Heart. Why are .β-Blocker Antiarrhythmics Superior?

Szentmiklósi¹,

Szentandrássy²,

Hegyi³

et al. 2014

CPD

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“…Gap junctional permeability values, which were obtained from 5 samples in each group, were assessed using double dye-loading (6). The ratio of Lucifer yellow and rhodamine-dextran stained areas was calculated using a computer-assisted image analysis system (Image-Pro Plus 3.0).…”

Section: Methodsmentioning

confidence: 99%

“…However, the mechanism behind this remains unclear. Recent studies have revealed that alterations in the amount of Cx43 and Cx43 phosphoralation status are important in the genesis of ventricular arrhythmias during acute MI (5,6). In the present study, we investigated the expression of Cx43 and the incidences of ventricular tachyarrhythmias [i.e., ventricular tachycardia (VT) and ventricular fibrillation (VF)] during acute MI in CMS rats.…”

Section: Introductionmentioning

confidence: 98%

Increased susceptibility to ischemia-induced ventricular tachyarrhythmias in depressed rats: Involvement of reduction of connexin 43

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. Connexin 43 (Cx43) has been reported to contribute to the occurrence of ventricular arrhythmias during myocardial ischemia (MI). In this study, we investigated the expression of Cx43 and the incidences of ventricular tachyarrhythmias [i.e., ventricular tachycardia (VT) and ventricular fibrillation (VF)] during acute MI in chronic mild stress (CMS) in rats. Male Sprague-Dawley (SD) control and CMS rats were assigned into a sham operation (SO) group and a MI group. Ventricular tachyarrhythmias were assessed and Cx43 protein expression was measured by Western blotting. During 30-min ischemia, the incidences of VT (7/12, 58.3%) and VF (5/12, 41.7%) in the CMS-MI group were significantly decreased compared with those in the control-MI group (12/12, 100.0% and 11/12, 91.7%; P<0.05). The amount of total Cx43 of the CMS-SO group was significantly decreased to approximately 50% compared with that of the control-SO group (P<0.05). The 30-min ischemia did not result in a significant change in the amount of total Cx43 (total Cx43 is defined as the non-phosphorylated Cx43 and phosphorylated Cx43) compared to that of the SO group in CMS rats (P>0.05). The amount of non-phosphorylated Cx43 in the CMS-MI group was markedly increased compared to that of the CMS-SO group (P<0.05), suggesting that the relative amount of phosphorylated Cx43 was significantly decreased in CMS rats. The gap junctional permeability in the CMS-MI group (50.4±4.9%) was significantly decreased compared with the normal non-ischemic value in the CMS-SO group (100%). The present study suggested that the incidence of ischemia-induced ventricular tachyarrhythmias was markedly increased in depressed rats, which may be associated with the reduction of Cx43 protein expression in the ventricle of depressed rats.

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“…The amount and distribution of Cx43 in the ventricles are significantly altered during ischemia Gutstein et al 2001;Vetterlein et al 2006). Previous studies have shown that Cx43 undergoes prominent dephosphorylation in ischemia-induced electrical uncoupling (Papp et al 2007;Jiang et al 2008), suggesting that the changes of Cx43 may contribute to the pathogenesis of ventricular arrhythmias during acute MI.…”

mentioning

confidence: 98%

Loss of Anti-Arrhythmic Effect of Vagal Nerve Stimulation on Ischemia-Induced Ventricular Tachyarrhythmia in Aged Rats

2011

Tohoku J. Exp. Med.

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Reduced vagal activity is associated with increased risk for life-threatening arrhythmia during myocardial ischemia (MI); conversely, the increase in vagal tone may provide protective effect against ventricular arrhythmias. In fact, vagal nerve stimulation (VNS) exerted an anti-arrhythmic effect by preserving connexin 43 (Cx43), a gap junction protein in ventricles, in a rat model of MI. We investigated the effects of VNS on ventricular tachyarrhythmia during acute MI and the expression of Cx43 in aged rats. Both adult (3-4 months) and aged (≥ 24 months) male rats were subjected to ischemia of 30 min. VNS was applied before ischemia either alone or in combination with atropine (0.5 mg/kg) or carbenoxolone, a gap junction inhibitor (10 mg/kg). During the 30-min ischemia, the incidence of ventricular tachycardia (VT) or ventricular fibrillation (VF) was higher in aged rats compared with adult rats. VNS significantly suppressed VT and VF in adult rats and these effects were eliminated by atropine or carbenoxolone. In contrast, VNS did not suppress VT and VF in the aged rats. Moreover, ischemia did not change the expression levels of total Cx43 protein in adult and aged rat ventricles. However, the expression level of total Cx43 protein was two times lower in sham-operated aged rats than that in sham-operated adult rats. Thus, in aged rats, loss of anti-arrhythmic effect of VNS is associated with reduced expression of Cx43 protein. These findings suggest that Cx43 may be an important target for inhibiting ischemia-induced VT in adult patients but not in aged patients.

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Gap junctional uncoupling plays a trigger role in the antiarrhythmic effect of ischaemic preconditioning

Cited by 45 publications

References 47 publications

Chemistry, Physiology, and Pharmacology of β.-Adrenergic Mechanisms in the Heart. Why are .β-Blocker Antiarrhythmics Superior?

Chemistry, Physiology, and Pharmacology of β.-Adrenergic Mechanisms in the Heart. Why are .β-Blocker Antiarrhythmics Superior?

Increased susceptibility to ischemia-induced ventricular tachyarrhythmias in depressed rats: Involvement of reduction of connexin 43

Loss of Anti-Arrhythmic Effect of Vagal Nerve Stimulation on Ischemia-Induced Ventricular Tachyarrhythmia in Aged Rats

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Gap junctional uncoupling plays a trigger role in the antiarrhythmic effect of ischaemic preconditioning

Cited by 45 publications

References 47 publications

Chemistry, Physiology, and Pharmacology of &#946;.-Adrenergic Mechanisms in the Heart. Why are .&#946;-Blocker Antiarrhythmics Superior?

Chemistry, Physiology, and Pharmacology of &#946;.-Adrenergic Mechanisms in the Heart. Why are .&#946;-Blocker Antiarrhythmics Superior?

Increased susceptibility to ischemia-induced ventricular tachyarrhythmias in depressed rats: Involvement of reduction of connexin 43

Loss of Anti-Arrhythmic Effect of Vagal Nerve Stimulation on Ischemia-Induced Ventricular Tachyarrhythmia in Aged Rats

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Chemistry, Physiology, and Pharmacology of β.-Adrenergic Mechanisms in the Heart. Why are .β-Blocker Antiarrhythmics Superior?

Chemistry, Physiology, and Pharmacology of β.-Adrenergic Mechanisms in the Heart. Why are .β-Blocker Antiarrhythmics Superior?