Cardiac repolarization. The long and short of it*

Antzelevitch, Charles

doi:10.1016/j.eupc.2005.05.010

Cited by 64 publications

(39 citation statements)

References 81 publications

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“…Considering that abnormal ventricular repolarization is tightly linked to a variety of arrhythmic manifestations, 15 the constitutive expression of CIRP in the heart and the CIRPdependency of cardiac repolarization may imply the critical involvement of CIRP in cardiac physiology and pathophysiology. Importantly, RNA-binding proteins are important molecules with universal biological activities.…”

Section: Discussionmentioning

confidence: 99%

Cold-Inducible RNA-Binding Protein Regulates Cardiac Repolarization by Targeting Transient Outward Potassium Channels

Xie

Huang

et al. 2015

Circulation Research

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Rationale: Cold-inducible RNA-binding protein (CIRP) is constitutively expressed at low levels across various tissues. It is rapidly upregulated by multiple stresses, underlying a general role for CIRP in organic adaptations to pathophysiological conditions. However, the role of CIRP in the heart remains unclear. Objective: To examine the biofunctions of CIRP in the mammalian heart. Methods and Results: Rats with targeted disruption of Cirp were generated using the TALEN (transcription activator-like effector nucleases)-based genome editing technique. The Cirp -knockout rats had structurally and functionally normal hearts. Resting ECG recordings revealed a short rate-corrected QT (QTc) interval in Cirp -null rats without any abnormalities in PR interval, RR interval or QRS waves as compared to wild-type animals. The shortened QTc interval from Cirp ablation was tightly linked to an abbreviated action potential duration in cardiac myocytes, which was attributable to increased transient outward potassium current ( I to ). Furthermore, our findings uncovered that CIRP protein selectively bonded to KCND2 and KCND3 mRNAs encoding the functional α-subunits of I to channel proteins. CIRP deficiency did not change the transcriptional activity of KCND2 or KCND3 , but it facilitated their translation. Cirp knockout had no effect on the functional expression of ion channels other than I to channels. Conclusions: CIRP modulates cardiac repolarization by negatively adjusting the expression and function of I to channels. Our study may open a window to decipher the potential function of RNA-binding proteins in bioelectric activity.

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Section: Discussionmentioning

confidence: 99%

Cold-Inducible RNA-Binding Protein Regulates Cardiac Repolarization by Targeting Transient Outward Potassium Channels

Xie

Huang

et al. 2015

Circulation Research

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“…Dysfunction of one of several of the ion channels can affect AP duration, and, depending on which particular ion channel is dysfunctional, the dispersion of repolarization may be increased [Antzelevitch, 2005]. These mechanisms are the pathophysiological basis of long QT syndrome (LQTS), short QT syndrome (SQTS), and some cases of AF.…”

Section: Pathogenetic Mechanism-in Overviewmentioning

confidence: 99%

“…Kv4.3 conducts the I to ; Kv11.1 conducts the I Kr current; Kv7.1 conducts the I Ks -current, and Kir2.1 conducts the I K1 -current. [Hu et al, 2009] state of inactivation from which it recovers more slowly; or accelerated inactivation of the sodium channel [Antzelevitch, 2005]. The G351V mutation is a classic example of ''typical'' BrS1 electrophysiology, as the mutation results in increased I Na current decay leading to reduced I Na current density [Vatta et al, 2002a].…”

Section: Brs1-mutations In Scn5amentioning

confidence: 99%

The genetic basis of Brugada syndrome: A mutation update

et al. 2009

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Brugada syndrome (BrS) is a condition characterized by a distinct ST-segment elevation in the right precordial leads of the electrocardiogram and, clinically, by an increased risk of cardiac arrhythmia and sudden death. The condition predominantly exhibits an autosomal dominant pattern of inheritance with an average prevalence of 5:10,000 worldwide. Currently, more than 100 mutations in seven genes have been associated with BrS. Loss-of-function mutations in SCN5A, which encodes the a-subunit of the Na v 1.5 sodium ion channel conducting the depolarizing I Na current, causes 15-20% of BrS cases. A few mutations have been described in GPD1L, which encodes glycerol-3-phosphate dehydrogenase-1 like protein; CACNA1C, which encodes the a-subunit of the Ca v 1.2 ion channel conducting the depolarizing I L,Ca current; CACNB2, which encodes the stimulating b2-subunit of the Ca v 1.2 ion channel; SCN1B and SCN3B, which, in the heart, encodes b-subunits of the Na v 1.5 sodium ion channel, and KCNE3, which encodes the ancillary inhibitory b-subunit of several potassium channels including the Kv4.3 ion channel conducting the repolarizing potassium I to current. BrS exhibits variable expressivity, reduced penetrance, and ''mixed phenotypes,'' where families contain members with BrS as well as long QT syndrome, atrial fibrillation, short QT syndrome, conduction disease, or structural heart disease, have also been described.

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“…11 In the Brugada syndrome, QT interval is largely unchanged, 12 and in the short QT syndrome, the QT interval abbreviates as a function of disease or drug concentration. 13 What they all have in common is the development of an augmented spatial dispersion of repolarization, TDR in particular. When TDR reaches the threshold for reentry, polymorphic VT develops.…”

Section: Long Qt Syndrome Brugada Syndrome and Conduction System DImentioning

confidence: 99%

Diagnostic and genetic aspects of the Brugada and other inherited arrhythmias syndromes

Antzelevitch

Wilde

Eckardt

et al. 2007

Journal of Electrocardiology

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Doctor Wilde, presenting on behalf of himself and Dr Eckardt, discussed the role of invasive and noninvasive tests for risk stratification of Brugada syndrome. Doctor Hiraoka, presenting on behalf of Y. Yokoyama, M. Takagi, N. Aihara, K. Aonuma, and the Japan Idiopathic Ventricular Fibrillation Study Investigators, further discussed the diagnostic criteria for the Brugada syndrome. Doctor Antzelevitch examined the hypothesis that amplification of spatial dispersion of repolarization in the form of transmural dispersion of repolarization underlies the development of life-threatening ventricular arrhythmias associated with inherited ion channelopathies including the long QT, short QT, and Brugada syndromes. Doctor Corrado discussed the relationship between channelopathies and heart muscle diseases. KeywordsArrhythmia; Sudden cardiac death; Ventricular tachycardia; Fibrillation; Electrophysiology; Channelopathies Role of invasive and noninvasive tests for stratification (A. Wilde and L. Eckardt)Brugada syndrome is increasingly recognized as a disease entity associated with sudden cardiac death (SCD), most often, in relatively young individuals without structural heart disease. The typical ECG is characterized by right precordial ST-segment elevation and discrete prolongation of diverse conduction parameters. Three types of ST-segment elevation are recognized, but only one, type 1 (ie, the 'coved-type' ST segment), is considered to be diagnostic of Brugada syndrome. When a type 1 ECG is associated with documented (or inducible) ventricular arrhythmias, premature SCD or similar ECGs in family members, or nocturnal agonal respiration, Brugada syndrome is diagnosed. 1,2 When the ECG is absent at baseline, drug challenge (iv flecainide, ajmaline procainamide, pilsicainide, or other sodium channel blockers) can unmask the ECG features. A genetic diagnosis can identify 18% to 30% of patients with SCN5A mutations. It is not essential for definitive diagnosis of the syndrome.

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Cardiac repolarization. The long and short of it*

Cited by 64 publications

References 81 publications

Cold-Inducible RNA-Binding Protein Regulates Cardiac Repolarization by Targeting Transient Outward Potassium Channels

Cold-Inducible RNA-Binding Protein Regulates Cardiac Repolarization by Targeting Transient Outward Potassium Channels

The genetic basis of Brugada syndrome: A mutation update

Diagnostic and genetic aspects of the Brugada and other inherited arrhythmias syndromes

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