Cardiac Sodium Channel Nav1.5 Mutations and Cardiac Arrhythmia

Song, Weihua; Shou, Weinian

doi:10.1007/s00246-012-0303-y

Cited by 48 publications

(30 citation statements)

References 58 publications

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“…Here is to be mentioned that there is a wide variety of SCN5 mutations, responsible for LQT3 syndrome, and depending on the site and type of mutation many parameters of Na + channel gating, including the rate of inactivation and recovery as well as the voltage dependence of activation and inactivation, may be altered, however, augmentation of I Na-late is a critical and common feature in all cases [39]. Since only a very small fraction of the total Na + cahnnel population may contribute μM TTX on APD.…”

Section: Discussionmentioning

confidence: 99%

Late sodium current in human, canine and guinea pig ventricular myocardium

Horváth

Hézsô

Szentandrássy

et al. 2020

Journal of Molecular and Cellular Cardiology

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Although late sodium current (I Na-late) has long been known to contribute to plateau formation of mammalian cardiac action potentials, lately it was considered as possible target for antiarrhythmic drugs. However, many aspects of this current are still poorly understood. The present work was designed to study the true profile of I Nalate in canine and guinea pig ventricular cells and compare them to I Na-late recorded in undiseased human hearts. I Na-late was defined as a tetrodotoxin-sensitive current, recorded under action potential voltage clamp conditions using either canonic-or self-action potentials as command signals. Under action potential voltage clamp conditions the amplitude of canine and human I Na-late monotonically decreased during the plateau (decrescendoprofile), in contrast to guinea pig, where its amplitude increased during the plateau (crescendo profile). The decrescendo-profile of canine I Na-late could not be converted to a crescendo-morphology by application of ramplike command voltages or command action potentials recorded from guinea pig cells. Conventional voltage clamp experiments revealed that the crescendo I Na-late profile in guinea pig was due to the slower decay of I Na-late in this species. When action potentials were recorded from multicellular ventricular preparations with sharp microelectrode, action potentials were shortened by tetrodotoxin, which effect was the largest in human, while smaller in canine, and the smallest in guinea pig preparations. It is concluded that important interspecies differences exist in the behavior of I Na-late. At present canine myocytes seem to represent the best model of human ventricular cells regarding the properties of I Na-late. These results should be taken into account when pharmacological studies with I Na-late are interpreted and extrapolated to human. Accordingly, canine ventricular tissues or myocytes are suggested for pharmacological studies with I Na-late inhibitors or modifiers. Incorporation of present data to human action potential models may yield a better understanding of the role of I Na-late in action potential morphology, arrhythmogenesis, and intracellular calcium dynamics. with physiological and pathological significance recognized long ago [1-3], its pathophysiological role in LQT3 [4] and heart failure [5-8] has been emphasized only in the last decades. I Na-late-as an inward current-contributes to plateau formation and is responsible for largely

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Section: Discussionmentioning

confidence: 99%

Late sodium current in human, canine and guinea pig ventricular myocardium

Horváth

Hézsô

Szentandrássy

et al. 2020

Journal of Molecular and Cellular Cardiology

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“…Additional lines of evidence 202 can be amassed to aid in the probabilistic interpretation of variants in JWS-susceptibility genes such as case phenotype, 203 segregation, functional studies, 204 in silico predictions, 205-208 variant type and location, 194 and variant frequency in cases and control databases. 193 Despite these aids, a large number of variants remain in “genetic purgatory,” and this number will only increase as the use of exome/genome sequencing becomes more utilized.…”

Section: Geneticsmentioning

confidence: 99%

J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge

et al. 2016

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“…TMCC inhibits cardiac sodium channel Nav1.5 expressed in a stable cell line. The sodium channel Nav1.5 is primarily expressed in cardiac muscles and Nav1.5 mutations are associated with cardiac arrhythmia (14). The present study analyzed the effect of TMCC on the cardiac sodium channel Nav1.5 in HEK cells stably expressing Nav1.5.…”

Section: Resultsmentioning

confidence: 99%

Acute and chronic effects of taurine magnesium coordination compound on cardiac sodium channel Nav1.5

Zhao

Yang

Yin

et al. 2017

Molecular Medicine Reports

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It has been previously demonstrated that taurine magnesium coordination compound (TMCC) produces antiarrhythmic effects in vivo. The present study investigated the acute and chronic effect of TMCC on sodium channels in HEK cells stably expressing human cardiac Nav1.5 sodium channels. The current amplitude, activation and inactivation kinetics, recovery time from inactivation, and use‑dependent block of sodium channels were analyzed using the whole‑cell patch clamp technique. Western blotting was used to analyze Nav1.5 expression following chronic TMCC treatment. In HEK cells expressing Nav1.5 channels, TMCC acutely inhibited Na+ currents in a dose‑dependent manner. In addition, acute application of TMCC shifted the activation and inactivation curves, and prolonged the recovery time from inactivation, but did not exhibit a use‑dependent block of Nav1.5. By contrast, chronic TMCC treatment only produced a use‑dependent block of Nav1.5 and downregulated Nav1.5 expression. The results of the present study suggested that TMCC may produce antiarrhythmic actions via acute inhibition of sodium channel currents and chronic downregulation of Nav1.5 expression.

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Cardiac Sodium Channel Nav1.5 Mutations and Cardiac Arrhythmia

Cited by 48 publications

References 58 publications

Late sodium current in human, canine and guinea pig ventricular myocardium

Late sodium current in human, canine and guinea pig ventricular myocardium

J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge

Acute and chronic effects of taurine magnesium coordination compound on cardiac sodium channel Nav1.5

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