Targeting intracellular calcium cycling in catecholaminergic polymorphic ventricular tachycardia: a theoretical investigation

Sung, Ruey J.; Lo, Chung Ping; Hsiao, Pi Yin; Tien, Hui-Chun

doi:10.1152/ajpheart.00696.2010

Cited by 8 publications

(2 citation statements)

References 39 publications

(98 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…25 waves, and subsequently cause DADs and TAs by activating I ti due to electrogenic Na + -Ca 2+ exchange current. 26,27) We found that 30 µm M-TMCA abolished Iso/BayK-induced eADs and significantly reduced the occurrence of DADs and TAs (Fig. 4).…”

Section: Resultsmentioning

confidence: 69%

Potential Antiarrhythmic Effect of Methyl 3,4,5-Trimethoxycinnamate, a Bioactive Substance from Roots of <i>Polygalae Radix</i>: Suppression of Triggered Activities in Rabbit Myocytes

Zhao

Fang

Xiao

et al. 2013

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

3,4,5-Trimethoxycinnamic acid (TMCA), methyl 3,4,5-trimethoxycinnamate (M-TMCA) and p-methoxycinnamic acid (PMCA) have been identified as the major bioactive components in the serum collected from rats treated with oral administration of Polygalae Radix ("YuanZhi," the roots of Polygala tenuifolia Willd.), a traditional Chinese medicine used to relieve insomnia, anxiety and heart palpitation. The present study was designed to investigate its direct electrophysiological effects on isolated ventricular myocytes from rabbits. Whole-cell configuration of the patch-clamp technique was used to measure action potential (AP) and membrane currents in single ventricular myocytes enzymatically isolated from adult rabbit hearts. Ca 2+ transients were recorded in myocytes loaded with the Ca 2+ indicator Fluo-4AM. Among three bioactive substances of Polygala metabolites, only M-TMCA (15-30 µm) significantly shortened action potential duration at 50% and 90% repolarization (APD 50 and APD 90 ) in cardiomyocytes in a concentration-dependent and a reversible manner. M-TMCA also inhibited L-type calcium current (I Ca,L ), but showed effect on neither transient outward potassium current (I to ) nor steady-state potassium current (I K,SS ). Furthermore, M-TMCA abolished isoprenaline plus BayK8644-induced early afterdepolarizations (EADs) and suppressed delayed afterdepolarizations (DADs) and triggered activities (TAs). This potential anti-arrhythmic effects were likely attributed by the inhibition of I Ca,L and the suppression of intracellular Ca 2+ transients, which consequently suppress the generation of transient inward current (I ti ). These findings suggest that M-TMCA may protect the heart from arrhythmias via its inhibitory effect on calcium channel.

show abstract

Section: Resultsmentioning

confidence: 69%

Potential Antiarrhythmic Effect of Methyl 3,4,5-Trimethoxycinnamate, a Bioactive Substance from Roots of <i>Polygalae Radix</i>: Suppression of Triggered Activities in Rabbit Myocytes

Zhao

Fang

Xiao

et al. 2013

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…Some patients need to resort to implantable cardioverter/defibrillators, left cardiac sympathetic denervation, and even to cardiac transplantation 24. Based on better understanding of the pathophysiology of CVPT, targeted pharmacotherapy appears to be very promising 43,44. Recently, flecainide therapy has been advocated to be efficacious in suppressing ventricular arrhythmias in CPVT as well as certain ATS patients 20,45–47.…”

Section: Altered Intracellular Ca2+ Cycling and Targeted Pharmacothermentioning

confidence: 99%

Gene mutations in cardiac arrhythmias: a review of recent evidence in ion channelopathies

Hsiao

Tien²,

Lo³

et al. 2013

TACG

Self Cite

View full text Add to dashboard Cite

Over the past 15 years, molecular genetic studies have linked gene mutations to many inherited arrhythmogenic disorders, in particular, “ion channelopathies”, in which mutations in genes encode functional units of ion channels and/or their transporter-associated proteins in patients without primary cardiac structural abnormalities. These disorders are exemplified by congenital long QT syndrome (LQTS), short QT syndrome, Brugada syndrome (BrS) and catecholaminergic polymorphic ventricular tachycardia (CPVT). Functional and pathophysiological studies have led to better understanding of the clinical spectrum, ion channel structures and cellular electrophysiology involving dynamics of intracellular calcium cycling in many subtypes of these disorders and more importantly, development of potentially more effective pharmacological agents and even curative gene therapy. In this review, we have summarized (1) the significance of unveiling mutations in genes encoding transporter-associated proteins as the cause of congenital LQTS, (2) the technique of catheter ablation applied at the right ventricular outflow tract may be curative for severely symptomatic BrS, (3) mutations with channel function modulated by protein Kinase A-dependent phosphorylation can be the culprit of CPVT mimicry in Andersen-Tawil syndrome (LQT7), (4) ablation of the ion channel anchoring protein may prevent arrhythmogenesis in Timothy syndrome (LQT8), (5) altered intracellular Ca2+ cycling can be the basis of effective targeted pharmacotherapy in CPVT, and (6) the technology of induced pluripotent stem cells is a promising diagnostic and research tool as it has become a new paradigm for pathophysiological study of patient- and disease-specific cells aimed at screening new drugs and eventual clinical application of gene therapy. Lastly, we have discussed (7) genotype-phenotype correlation in relation to risk stratification of patients with congenital LQTS in clinical practice.

show abstract

Catecholaminergic Polymorphic Ventricular Tachycardia

Kukavica

Trancuccio

Mazzanti

et al. 2021

Sport-Related Sudden Cardiac Death

View full text Add to dashboard Cite

Targeting intracellular calcium cycling in catecholaminergic polymorphic ventricular tachycardia: a theoretical investigation

Cited by 8 publications

References 39 publications

Potential Antiarrhythmic Effect of Methyl 3,4,5-Trimethoxycinnamate, a Bioactive Substance from Roots of <i>Polygalae Radix</i>: Suppression of Triggered Activities in Rabbit Myocytes

Potential Antiarrhythmic Effect of Methyl 3,4,5-Trimethoxycinnamate, a Bioactive Substance from Roots of <i>Polygalae Radix</i>: Suppression of Triggered Activities in Rabbit Myocytes

Gene mutations in cardiac arrhythmias: a review of recent evidence in ion channelopathies

Catecholaminergic Polymorphic Ventricular Tachycardia

Contact Info

Product

Resources

About