Atrial Fibrillation in the Goat Induces Changes in Monophasic Action Potential and mRNA Expression of Ion Channels Involved in Repolarization

Velden, Huub M.W. van der; Zee, Lucie van der; Wijffels, Maurits C.E.F.; Leuven, Carlo Van; Dorland, Rick; Vos, Marc A.; Jongsma, Habo J.; Allessie, Maurits A.

doi:10.1046/j.1540-8167.2000.01262.x

Cited by 63 publications

(6 citation statements)

References 22 publications

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“…The molecular mechanisms of ion channel remodeling in AF, such as down-regulation of mRNA and protein functional expressions of Kv4.3, the α1c subunit of L-type Ca 2+ channels, and the α-subunit of cardiac Na + channels were observed through the dog chronic AF models and cultured atrial cardiomyocytes applied by electrical pacing 16,37,38. So far, there are no reports about the ion channel remodeling in intact mice with AF.…”

Section: Discussionmentioning

confidence: 99%

“…In patients with AF, increased atrial rates enhance cardiomyocyte Ca 2+ influx with each action potential (AP). To prevent potentially cytotoxic Ca 2+ overload, atrial cardiomyocytes limit Ca 2+ influx through accelerating I Ca-L inactivation and down-regulation of mRNA encoding I Ca-L , consequently resulting in decrease in both I Ca-L and atrial AP duration (APD), which, in turn, relatively increase in ERP 16,17. In clinical therapy of AF, current Ca 2+ channel blockers are frequently used to reduce Ca 2+ overload with the expectation that prevents arrhythmogenic remodeling, however, it actually aggregates down-regulation of I Ca-L in the atrium so as to increase the risk of ventricular arrhythmia and does not show a beneficial effects on AF 18,19.…”

Section: Introductionmentioning

confidence: 99%

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Matrine Inhibits Pacing Induced Atrial Fibrillation by Modulating I_KM3 and I_Ca-L

Zhou¹,

Xu²,

Ruyi³

et al. 2012

Int. J. Biol. Sci.

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Aim: To elucidate the protective effects of Matrine on atrial fibrillation (AF) induced by electric pacing in mice and underlying molecular and ion channel mechanisms.Methods: AF was introduced by electric pacing in mice and the incidence and duration of AF were evaluated. Functional expression of M3 receptor (M3-R) and Cav1.2 were explored by western and Real-time PCR, action potential (AP) and the density of (IKM3) L-type calcium channel (ICa-L) were both recorded using whole-cell patch in isolated atrial cardiomyocytes.Results: In control group, incidence and duration of AF induced by electric pacing were 50 ± 17% and 3.68 ± 1.84 s, respectively; after application of carbachol 50 µg/kg both incidence and duration of AF were significantly increased to 86 ± 24% and 65.2 ± 29.0 s. Compared with control group, pretreatment of Matrine for 15 days significantly reduced AF incidence and duration in dose-dependent manner. Atrial membrane-protein expression of M3-R was decreased and membrane Cav1.2 expression was up-regulated. In single Matrine-treated atrial cardiomyocyte the density of IKM3 was significantly decreased by 39% as well compared with control group, P < 0.05, whereas, ICa-L density of atrium was increased by 40%.Conclusion: These data demonstrated at the first time that the anti-AF effects of Matrine may due, at least in part, to down-regulation of IKM3 density and M3-R expression and up-regulation of ICa-L density and α1C/Cav1.2 expression.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Matrine Inhibits Pacing Induced Atrial Fibrillation by Modulating I_KM3 and I_Ca-L

Zhou¹,

Xu²,

Ruyi³

et al. 2012

Int. J. Biol. Sci.

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“…Thus, atrial tachypacing decreased Na v 1.5 mRNA, I Na , and θ over several weeks in canine models (Gaspo et al, 1997; Yue et al, 1999). In contrast, the development of AF does not further reduce atrial I Na (Yagi et al, 2002) or Na v 1.5 mRNA (van der Velden et al, 2000) in canine and goat models, respectively.…”

Section: The Na+ Channel and Its Relationship To Inamentioning

confidence: 98%

Determinants of myocardial conduction velocity: implications for arrhythmogenesis

King¹,

Huang²,

Fraser³

2013

Front. Physiol.

172

167

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Slowed myocardial conduction velocity (θ) is associated with an increased risk of re-entrant excitation, predisposing to cardiac arrhythmia. θ is determined by the ion channel and physical properties of cardiac myocytes and by their interconnections. Thus, θ is closely related to the maximum rate of action potential (AP) depolarization [(dV/dt)max], as determined by the fast Na+ current (INa); the axial resistance (ra) to local circuit current flow between cells; their membrane capacitances (cm); and to the geometrical relationship between successive myocytes within cardiac tissue. These determinants are altered by a wide range of pathophysiological conditions. Firstly, INa is reduced by the impaired Na+ channel function that arises clinically during heart failure, ischemia, tachycardia, and following treatment with class I antiarrhythmic drugs. Such reductions also arise as a consequence of mutations in SCN5A such as those occurring in Lenègre disease, Brugada syndrome (BrS), sick sinus syndrome, and atrial fibrillation (AF). Secondly, ra, may be increased due to gap junction decoupling following ischemia, ventricular hypertrophy, and heart failure, or as a result of mutations in CJA5 found in idiopathic AF and atrial standstill. Finally, either ra or cm could potentially be altered by fibrotic change through the resultant decoupling of myocyte–myocyte connections and coupling of myocytes with fibroblasts. Such changes are observed in myocardial infarction and cardiomyopathy or following mutations in MHC403 and SCN5A resulting in hypertrophic cardiomyopathy (HCM) or Lenègre disease, respectively. This review defines and quantifies the determinants of θ and summarizes experimental evidence that links changes in these determinants with reduced myocardial θ and arrhythmogenesis. It thereby identifies the diverse pathophysiological conditions in which abnormal θ may contribute to arrhythmia.

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“…The decrease in I Ca(L) seen early in response to rapid atrial stimulation continues in response to repeated episodes of AF (Yue et al, 1997 ; Van Wagoner et al, 1999 ; Workman et al, 2001 ; Yagi et al, 2002 ; Christ et al, 2004 ; Lenaerts et al, 2009 ; Voigt et al, 2012 ), potentially caused by lower levels of mRNA for the alpha subunit (Brundel et al, 1999 , 2001 ; Lai et al, 1999 ; Van Gelder et al, 1999 ; van der Velden et al, 2000b ; Gaborit et al, 2005 ), reduced LTCC protein expression (Brundel et al, 1999 , 2001 ; Lenaerts et al, 2009 ), a shift in single channel gating (Lenaerts et al, 2009 ) and potentially a reduction in single channel open probability due to reduced phosphorylation (Christ et al, 2004 ). The time course over which these changes occur has been variably reported as between 2 and 6 months (Van Gelder et al, 1999 ; van der Velden et al, 2000b ), which may reflect differences in AF burden between studies. Studies investigating LTCCs during the progression of AF report decreased expression in persistent AF but not in paroxysmal AF suggesting I Ca(L) might decrease over the time course of the disease (Brundel et al, 1999 ; Van Gelder et al, 1999 ).…”

Section: The Pathophysiology Of Atrial Fibrillationmentioning

confidence: 99%

Calcium in the Pathophysiology of Atrial Fibrillation and Heart Failure

et al. 2018

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Atrial fibrillation (AF) is commonly associated with heart failure. A bidirectional relationship exists between the two—AF exacerbates heart failure causing a significant increase in heart failure symptoms, admissions to hospital and cardiovascular death, while pathological remodeling of the atria as a result of heart failure increases the risk of AF. A comprehensive understanding of the pathophysiology of AF is essential if we are to break this vicious circle. In this review, the latest evidence will be presented showing a fundamental role for calcium in both the induction and maintenance of AF. After outlining atrial electrophysiology and calcium handling, the role of calcium-dependent afterdepolarizations and atrial repolarization alternans in triggering AF will be considered. The atrial response to rapid stimulation will be discussed, including the short-term protection from calcium overload in the form of calcium signaling silencing and the eventual progression to diastolic calcium leak causing afterdepolarizations and the development of an electrical substrate that perpetuates AF. The role of calcium in the bidirectional relationship between heart failure and AF will then be covered. The effects of heart failure on atrial calcium handling that promote AF will be reviewed, including effects on both atrial myocytes and the pulmonary veins, before the aspects of AF which exacerbate heart failure are discussed. Finally, the limitations of human and animal studies will be explored allowing contextualization of what are sometimes discordant results.

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Atrial Fibrillation in the Goat Induces Changes in Monophasic Action Potential and mRNA Expression of Ion Channels Involved in Repolarization

Cited by 63 publications

References 22 publications

Matrine Inhibits Pacing Induced Atrial Fibrillation by Modulating I_KM3 and I_Ca-L

Matrine Inhibits Pacing Induced Atrial Fibrillation by Modulating I_KM3 and I_Ca-L

Determinants of myocardial conduction velocity: implications for arrhythmogenesis

Calcium in the Pathophysiology of Atrial Fibrillation and Heart Failure

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Atrial Fibrillation in the Goat Induces Changes in Monophasic Action Potential and mRNA Expression of Ion Channels Involved in Repolarization

Cited by 63 publications

References 22 publications

Matrine Inhibits Pacing Induced Atrial Fibrillation by Modulating IKM3 and ICa-L

Matrine Inhibits Pacing Induced Atrial Fibrillation by Modulating IKM3 and ICa-L

Determinants of myocardial conduction velocity: implications for arrhythmogenesis

Calcium in the Pathophysiology of Atrial Fibrillation and Heart Failure

Contact Info

Product

Resources

About

Matrine Inhibits Pacing Induced Atrial Fibrillation by Modulating I_KM3 and I_Ca-L

Matrine Inhibits Pacing Induced Atrial Fibrillation by Modulating I_KM3 and I_Ca-L