Ion channels, long QT syndrome and arrhythmogenesis in ageing.


:Ageing is associated with increased prevalences of both atrial and ventricular arrhythmias, reflecting disruption of the normal sequence of ion channel activation and inactivation generating the propagated cardiac action potential. Experimental models with specific ion channel genetic modifications have helped clarify the interacting functional roles of ion channels and how their dysregulation contributes to arrhythmogenic processes at the cellular and systems level. They have also investigated interactions between these ion channel abnormalities and age-related processes in producing arrhythmic tendency. Previous reviews have explored the relationships between age and loss-of-function Nav 1.5 mutations in producing arrhythmogenicity. The present review now explores complementary relationships arising from gain-of-function Nav 1.5 mutations associated with long QT3 (LQTS3). LQTS3 patients show increased risks of life-threatening ventricular arrhythmias, particularly after 40 years of age, consistent with such interactions between the ion channel abnormailities and ageing. In turn clinical evidence suggests that ageing is accompanied by structural, particularly fibrotic, as well as electrophysiological change. These abnormalities may result from biochemical changes producing low-grade inflammation resulting from increased production of reactive oxygen species and superoxide. Experimental studies offer further insights into the underlying mechanisms underlying these phenotypes. Thus, studies in genetically modified murine models for LQTS implicated action potential recovery processes in arrhythmogenesis resulting from functional ion channel abnormalities. In addition, ageing wild type (WT) murine models demonstrated both ion channel alterations and fibrotic changes with ageing. Murine models then suggested evidence for interactions between ageing and ion channel mutations and provided insights into potential arrhythmic mechanisms inviting future exploration.


Jeevaratnam K,Chadda KR,Salvage SC,Valli H,Ahmad S,Grace AA,Huang CL




Has Abstract


2017-12-01 00:00:00








44 Suppl 1


  • Single-unit sympathetic discharge pattern in pathological conditions associated with elevated cardiovascular risk.

    abstract::1. Although measuring the rate of firing of multi-unit muscle sympathetic nerve activity (MSNA) has provided important information in many aspects of cardiovascular medicine, measuring single-unit vasoconstrictor activity provides a better understanding of the possible mechanisms underlying disturbed sympathetic nervo...

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  • Chlamydia pneumoniae induces a pro-inflammatory phenotype in murine vascular smooth muscle cells independently of elevating reactive oxygen species.

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    pub_type: 杂志文章


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    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


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  • Effects of FR139317 on renal responses to acute nitric oxide blockade in anaesthetized rats.

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    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


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  • Beta2-adrenoceptor polymorphisms and obstructive airway diseases: important issues of study design.

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    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章,评审


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    更新日期:2007-10-01 00:00:00

  • Opioid receptors mediate inotropic and depressor effects of apelin in rats with 2K1C-induced chronic renovascular hypertension.

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    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Rostamzadeh F,Najafipour H,Yeganeh-Hajahmadi M,Joukar S

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  • Significance of serine proteinase and matrix metalloproteinase systems in the destruction of human articular cartilage.

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    pub_type: 杂志文章


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    pub_type: 杂志文章,评审


    authors: White PJ

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  • Key mechanisms underlying netrin-1 prevention of impaired spatial and object memory in Aβ1-42 CA1-injected rats.

    abstract::Alzheimer's disease (AD) is a neurodegenerative disorder with an incompletely defined aetiology that is associated with memory and cognitive impairment. Currently available therapeutics only provide temporary assistance with symptoms. In spite of plentiful research in the field and the generation of thousands of studi...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Zamani E,Parviz M,Roghani M,Mohseni-Moghaddam P

    更新日期:2019-01-01 00:00:00

  • Hypoxia-reoxygenation-induced apoptosis in cultured neonatal rat cardiomyocyets and the protective effect of prostaglandin E.

    abstract::The aim of the present study was to investigate the effect of prostaglandin (PG) E1 on hypoxia/re-oxygenation (H/R) apoptosis and the expression of bcl-2 and bax in cultured neonatal rat cardiomyocytes. The H/R model was made using the first generation of cultured neonatal rat cardiomyocytes. Hypoxia/re-oxygenation ap...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Ma XQ,Fu RF,Feng GQ,Wang ZJ,Ma SG,Weng SA

    更新日期:2005-12-01 00:00:00

  • Effects of mild aerobic physical exercise on membrane fluidity of erythrocytes in essential hypertension.

    abstract::1. The present study was undertaken to investigate the effects of aerobic physical exercise on membrane function in mild essential hypertension. 2. Hypertensive patients were divided into an exercise group (n = 8) and a non-exercise (control) group (n = 8). Physical exercise within the intensity of the anaerobic thres...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Tsuda K,Yoshikawa A,Kimura K,Nishio I

    更新日期:2003-05-01 00:00:00

  • Nephropreventing effect of hypoxia-inducible factor 1α in a rat model of ischaemic/reperfusion acute kidney injury.

    abstract::Acute kidney injury (AKI) occurs in 5% of hospitalized patients and in 50% of sepsis patients with acute renal dysfunction. However, there have been no safe and effective therapeutic strategies. The hypoxia condition is closely related to renal injury and function under AKI. As hypoxia-inducible factor 1α (HIF-1α) is ...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Wang H,Liu N,Li R,Tian J,Hu W,Zhang J

    更新日期:2018-10-01 00:00:00

  • The effect of hypertensive episodes and cardiac hypertrophy on the canine cardiac baroreflex.

    abstract::1. Left ventricular (LV) hypertrophy has been implicated in the reduction of baroreflex sensitivity present in hypertension. The aim of the current study was to investigate the mean arterial pressure-heart rate reflex (MAP-HR) in a model which induced left ventricular hypertrophy but no sustained blood pressure elevat...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


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    更新日期:1994-01-01 00:00:00

  • Control of intravascular volume during pregnancy.

    abstract::1. We wished to determine whether, during pregnancy, there is reduced renal response to atrial distension, whether secretion of atrial natriuretic factor (ANF) is suppressed and whether neural input from the atrial volume receptors to the central nervous system is altered. 2. Conscious, chronically instrumented female...

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    pub_type: 杂志文章


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  • Stretch-activated channels in stretch-induced muscle damage: role in muscular dystrophy.

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    journal_title:Clinical and experimental pharmacology & physiology



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    更新日期:2004-08-01 00:00:00

  • Systemic and regional haemodynamic responses to isoprenaline in conscious renal hypertensive rabbits.

    abstract::1. Using the electromagnetic flow probe and the radioactive microsphere technique, systemic and regional haemodynamic variables were measured in conscious normotensive and hypertensive rabbits. The rabbits were made hypertensive by unilateral nephrectomy combined with cellophane-wrapping of the remaining kidney and sy...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


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  • A study of the relationship between cardiac beta-adrenoceptor blockade and intrinsic sympathomimetic activity in rats depleted of catecholamines.

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    pub_type: 杂志文章


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  • Effects of apolipoprotein A gene polymorphisms on lipoprotein (a) concentrations in Japanese.

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    pub_type: 杂志文章


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