Abstract：
:Cardiac output and rhythm depend on the release and the take-up of calcium from the sarcoplasmic reticulum (SR). Excessive diastolic calcium leak from the SR due to dysfunctional calcium release channels (RyR2) contributes to the formation of delayed after-depolarizations, which underlie the fatal arrhythmias that occur in heart failure and inherited syndromes. Calmodulin (CaM) is a calcium-binding protein that regulates target proteins and acts as a calcium sensor. CaM is comprised of two calcium-binding EF-hand domains and a flexible linker. CaM is an accessory protein that partially inhibits RyR2 channel activity. CaM is critical for normal cardiac function, and altered CaM binding and efficacy may contribute to defects in SR calcium release. The present paper reviews CaM binding to RyR2 and how it regulates RyR2 channel activity. It then goes on to review how mutations in the CaM amino acid sequence give rise to inherited syndromes such as Catecholaminergic Polymorphic Ventricular Tachychardia (CPVT) and long QT syndrome (LQTS). In addition, the role of reduced CaM binding to RyR2 that results from RyR2 phosphorylation or from oxidation of either RyR2 or CaM contributes to the progression of heart failure is reviewed. Finally, this manuscript reviews recent evidence that CaM binding to RyR2 is required for the inhibitory action of a pharmaceutical agent (dantrolene) on RyR2. Dantrolene is a clinically used muscle relaxant that has recently been found to exert antiarrhythmic effects against SR Ca2+ overload arrhythmias.
journal_name
Clin Exp Pharmacol Physioljournal_title
Clinical and experimental pharmacology & physiologyauthors
Walweel K,Oo YW,Laver DRdoi
10.1111/1440-1681.12669subject
Has Abstractpub_date
2017-01-01 00:00:00pages
135-142issue
1eissn
0305-1870issn
1440-1681journal_volume
44pub_type
杂志文章,评审abstract：:Autophagy promotes cell survival or induces apoptosis in cancer cells. While SIRT1 and AMPK induce autophagy in both normal and cancer cells, Akt and mTOR can inhibit it. Calycosin, a methoxyisoflavone, protects against several types of solid tumours including colorectal cancer. However, the mechanisms behind the anti...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/1440-1681.13133
更新日期：2019-10-01 00:00:00
abstract：:Heart rate recovery (HRR) describes the rapid deceleration of heart rate after strenuous exercise and is an indicator of parasympathetic tone. A reduction in parasympathetic tone occurs in patients with congestive heart failure, resulting in prolonged HRR. Acetylcholinesterase inhibitors, such as pyridostigmine, can e...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/1440-1681.12773
更新日期：2017-08-01 00:00:00
abstract：:This study hypothesized that different types of anaesthesia management would result in similar postoperative sleep quality. In this prospective single-blind investigation, 219 patients undergoing elective thoracic surgery were randomized into three arms: general anaesthesia, as the control group (group C); general ana...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章,随机对照试验
doi：10.1111/1440-1681.12530
更新日期：2016-03-01 00:00:00
abstract：:1. Stimulation of the mesolimbic dopamine system, by micro-injection of the substance P analogue [pGlu5,MePhe8,Sar9] substance P (DiMe-C7) into the ventral tegmental area induced a prolonged increase in blood pressure and circulating levels of vasopressin. 2. In the present study, this treatment produced a significant...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1998.tb02264.x
更新日期：1998-07-01 00:00:00
abstract：:1. In a number of species, high concentrations of angiotensin II (AngII) receptors have been found in the rostral ventrolateral medulla (RVLM) in the hindbrain, which is an important region involved in the modulation of sympathetic vasomotor tone. The present review describes studies in which the contribution of angio...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章,评审
doi：10.1111/j.1440-1681.1996.tb02820.x
更新日期：1996-09-01 00:00:00
abstract：:The currently available chemotherapeutic regimens against gastric cancer are not very effective, leading to high recurrence and poor survival. Resveratrol is a naturally occurring polyphenol with potent apoptosis-inducing activity. However, the mechanism underlying its actions remains unknown. In the present study, hu...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.2011.05660.x
更新日期：2012-03-01 00:00:00
abstract：:1. Inflammation, particularly the pro-inflammatory cytokine tumour necrosis factor (TNF), increases necrosis of skeletal muscle. Depletion of inflammatory cells, such as neutrophils, cromolyn blockade of mast cell degranulation or pharmacological blockade of TNF reduces necrosis of dystrophic myofibres in the mdx mous...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章,评审
doi：10.1111/j.1440-1681.2007.04868.x
更新日期：2008-07-01 00:00:00
abstract：:1. Renin mRNA is present in the kidney and, in lower concentrations, in many extrarenal tissues and serves as an index of renin gene activity, as well as potential renin or prorenin synthesis in cell populations within those tissues. Unfortunately the quantity can be very low. 2. A new, highly sensitive technique is d...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1991.tb01463.x
更新日期：1991-05-01 00:00:00
abstract：:1. The endogenous production of and/or the bioavailability of nitric oxide (NO) is decreased in pulmonary hypertensive diseases. L-arginine (L-arg) is the substrate for NO synthase (NOS). L-arg is transported into cells via the cationic amino acid transporters (CAT), of which there are two isoforms in endothelial cell...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.2011.05609.x
更新日期：2011-12-01 00:00:00
abstract：:1. The influence of the intact kidney on blood pressure, extracellular fluid volume (ECF, ferrocyanide space) and ECF volume distribution was studied in rats 60 days after constriction of the contralateral renal artery. 2. Renal artery constriction increased both blood pressure and ECF levels. The rise of both variabl...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1979.tb00033.x
更新日期：1979-09-01 00:00:00
abstract：:Hyperhomocysteine has become a critical risk for atherosclerosis and can stimulate proliferation and migration of vascular smooth muscle cells (VSMCs). N-methyl-D-aspartic acid receptor (NMDAR) is a receptor of homocysteine and mediates the effects of homocysteine on VSMCs. Bioinformatics analysis has shown NMDAR is a...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/1440-1681.12611
更新日期：2016-10-01 00:00:00
abstract：:1. The development of microneurography, in which an insulated tungsten microelectrode is inserted into an accessible peripheral or cranial nerve in awake human subjects, has allowed detailed analyses of the signalling capacities of single mechanoreceptive afferents from the skin, muscles and joints. For example, we kn...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章,评审
doi：10.1111/j.1440-1681.2005.04143.x
更新日期：2005-01-01 00:00:00
abstract：:This paper attempts to provide a short review of the evidence for: 1. Increased platelet production of thromboxane A2 and reduced vascular production of prostacyclin in the human and also animal models of diabetes. 2. Reduced depressor responsiveness to arachidonic acid of anaesthetized alloxan- and streptozotocin-ind...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章,评审
doi：10.1111/j.1440-1681.1992.tb00391.x
更新日期：1992-01-01 00:00:00
abstract：:Tiron functions as an effective antioxidant alleviating the intracellular reactive oxygen species (ROS) or the acute toxic metal overload. Previous studies have shown that cardiac myocyte apoptosis can be effectively inhibited by tiron administration in streptozotocin (STZ)-induced diabetic rats, primary neonatal rat ...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/1440-1681.12762
更新日期：2017-07-01 00:00:00
abstract：:Afferent splanchnic nerve stimulation with different frequencies in Wistar Kyoto rats caused depressor and pressor responses depending on the frequency employed. Similar visceral afferent activation in spontaneously hypertensive rats caused depressor responses at all frequencies of stimulation. It is suggested that th...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1985.tb00300.x
更新日期：1985-01-01 00:00:00
abstract：:1. The present study investigated whether the somatostatin receptor (SSTR) agonist, octreotide, could inhibit the activation of dorsal skin afferent fibres induced by local injection of capsaicin in the rat. 2. Single unit activity from Aδ mechano-heat sensitive (AMH; n = 41) and C mechano-heat sensitive (CMH; n = 30)...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.2011.05542.x
更新日期：2011-08-01 00:00:00
abstract：:The prostaglandin synthesis inhibitor diclofenac sodium has been compared with a placebo in the treatment of primary nocturnal enuresis in a double-blind crossover trial. Twenty patients were entered: 14 female, six male; age range 6-17 years. The results showed that diclofenac sodium was significantly more effective ...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1440-1681.1986.tb00327.x
更新日期：1986-02-01 00:00:00
abstract：:1. Levodopa markedly reduces parkinsonism during the first years of treatment. However, with continued therapy the response to levodopa becomes erratic and is complicated by involuntary movements. To improve the therapy of parkinsonism, the challenge is to understand why fluctuations in response develop and, once deve...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1995.tb01946.x
更新日期：1995-11-01 00:00:00
abstract：:1. The spinal sympathetic outflow (C7-T2) of pithed male Wistar rats was electrically stimulated (30-50 V, 0.5 ms, 0.1-1.0 Hz) and heart rate and arterial blood pressure were recorded. D-Tubocurarine (1 mg/kg) and atropine (1 mg/kg) were administered intravenously (i.v.) to reduce voluntary and parasympathetic nerve a...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1988.tb01036.x
更新日期：1988-12-01 00:00:00
abstract：:1. Currently, there is no satisfactory treatment for pulmonary fibrosis. Emodin, a component in Chinese herbs, has been shown to have an antifibrotic effect on pancreatic fibrosis and liver fibrosis. In the present study, we tested the hypothesis that emodin may attenuate the development of pulmonary fibrosis. 2. Mice...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.2008.05048.x
更新日期：2009-02-01 00:00:00
abstract：:Peptidyl-prolyl cis/trans isomerases (PPIases) are a conserved group of enzymes that catalyse the conversion between cis and trans conformations of proline imidic peptide bonds. These enzymes play critical roles in regulatory mechanisms of cellular function and pathophysiology of disease. There are three different cla...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章,评审
doi：10.1111/1440-1681.12335
更新日期：2015-02-01 00:00:00
abstract：:Subendocardial viability ratio (SEVR) is a reliable index of myocardial supply-workload balance. This study sought to investigate whether overweight/obese children and adolescents have altered SEVR and to identify which are the associated factors. This cross-sectional study involved 789 individuals. Central haemodynam...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 信件
doi：10.1111/1440-1681.12922
更新日期：2018-05-01 00:00:00
abstract：:1. In rat isolated tail arteries and atria in which transmitter stores are labelled with (3H)-noradrenaline, isoprenaline in low concentrations facilitates the stimulation-induced efflux of tritium. 2. This effect is dependent on the frequency and duration of electrical stimulation, being observed only at low frequenc...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1980.tb00114.x
更新日期：1980-09-01 00:00:00
abstract：:1. In the present study, the effects of the administration of adenosine on absence seizures were investigated in the Wistar Albino Glaxo/Rijswijk (WAG/Rij) strain of rats, which are an adequate model for human absence epilepsy. 2. After baseline electroencephalogram (EEG) recording, adenosine was injected intraperiton...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1046/j.1440-1681.2001.03499.x
更新日期：2001-08-01 00:00:00
abstract：:1. The present report documents evidence suggesting that endothelin (ET) is a mediator and modulator of post-ganglionic sympathetic neuronal development. 2. Endothelin is produced by post-ganglionic neurons and by cells adjacent to these neurons. 3. Post-ganglionic sympathetic neurons express functional receptors for ...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章,评审
doi：10.1046/j.1440-1681.1999.03179.x
更新日期：1999-12-01 00:00:00
abstract：:1. The present paper reviews the toxic dinoflagellates found in Singapore waters that produce toxins that can accumulate through marine food chains to cause seafood poisonings. 2. Singapore waters contain dinoflagellate species linked to three types of seafood poisoning: paralytic shellfish poisoning, diarrhetic shell...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章,评审
doi：10.1046/j.1440-1681.2002.03724.x
更新日期：2002-09-01 00:00:00
abstract：:1. The renal medulla plays an important role in regulating body sodium and fluid balance and blood pressure homeostasis through its unique structural relationships and interactions between renomedullary interstitial cells (RMIC), renal tubules and medullary vasculature. 2. Several endocrine and/or paracrine factors, i...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章,评审
doi：10.1046/j.1440-1681.2000.03277.x
更新日期：2000-07-01 00:00:00
abstract：:1. Most studies examining the effect of angiotensin-converting enzyme (ACE) inhibitors on atherosclerosis in experimental animals have used doses well in excess of those given clinically. 2. Using a rabbit model of cholesterol-induced atherosclerosis characterized by subendothelial lipid accumulations ('juvenile fatty...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章,评审
doi：10.1111/j.1440-1681.1996.tb03038.x
更新日期：1996-08-01 00:00:00
abstract：:1. The most usual form of chronic hypoxia in humans is the intermittent hypoxia resulting from obstructive sleep apnoea (OSA). The OSA syndrome is a highly prevalent sleep breathing disorder that is considered an independent risk factor for hypertension and cardiovascular diseases. Endothelial dysfunction, oxidative s...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章,评审
doi：10.1111/j.1440-1681.2009.05213.x
更新日期：2009-12-01 00:00:00
abstract：:The aim of this study was to determine whether the kaliuresis associated with glucocorticoids is due to a direct tubular action or is secondary to effects of glucocorticoids on distal tubule flow. A whole kidney technique was used to avoid the problem, inherent in microperfusion and micropuncture studies, of deciding ...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1987.tb00956.x
更新日期：1987-01-01 00:00:00
