Clinical disability following trauma or disease to the spinal cord often involves the loss of vital white matter elements including axons and glia.Although excessive Cais an established driver of axonal degeneration,t...Clinical disability following trauma or disease to the spinal cord often involves the loss of vital white matter elements including axons and glia.Although excessive Cais an established driver of axonal degeneration,therapeutically targeting externally sourced Cato date has had limited success in both basic and clinical studies.Contributing factors that may underlie this limited success include the complexity of the many potential sources of Caentry and the discovery that axons also contain substantial amounts of stored Cathat if inappropriately released could contribute to axonal demise.Axonal Castorage is largely accomplished by the axoplasmic reticulum that is part of a continuous network of the endoplasmic reticulum that provides a major sink and source of intracellular Cafrom the tips of dendrites to axonal terminals.This“neuron-within-a-neuron”is positioned to rapidly respond to diverse external and internal stimuli by amplifying cytosolic Calevels and generating short and long distance regenerative Cawaves through Cainduced Carelease.This review provides a glimpse into the molecular machinery that has been implicated in regulating ryanodine receptor mediated Carelease in axons and how dysregulation and/or overstimulation of these internodal axonal signaling nanocomplexes may directly contribute to Ca-dependent axonal demise.Neuronal ryanodine receptors expressed in dendrites,soma,and axonal terminals have been implicated in synaptic transmission and synaptic plasticity,but a physiological role for internodal localized ryanodine receptors remains largely obscure.Plausible physiological roles for internodal ryanodine receptors and such an elaborate internodal binary membrane signaling network in axons will also be discussed.展开更多
BACKGROUND:Calcium calmodulin-dependent kinase II(CaMKII) can be more active in patients with left ventricular hypertrophy(LVH),which in turn causes phosphorylation of ryanodine receptors,resulting in inactivation and...BACKGROUND:Calcium calmodulin-dependent kinase II(CaMKII) can be more active in patients with left ventricular hypertrophy(LVH),which in turn causes phosphorylation of ryanodine receptors,resulting in inactivation and the instability of intracellular calcium homeostasis.The present study aimed to determine the effect of CaMKII-ryanodine receptor pathway signaling in rabbits with left ventricular hypertrophy and triggered ventricular arrhythmia.METHODS:Forty New Zealand rabbits were randomized into four groups(10 per group):sham group,LVH group,KN-93 group(LVH+KN-93),and ryanodine group(LVH+ryanodine).Rabbits in the LVH,KN-93,and ryanodine groups were used to establish a left ventricular hypertrophy model by the coarctation of the abdominal aorta,while those in the sham group did not undergo the coarctation.After eight weeks,action potentials(APs) were recorded simultaneously in the endocardium and epicardium,and a transmural electrocardiogram(ECG) was also recorded in the rabbit left ventricular wedge model.Drugs were administered to the animals in the KN-93 and ryanodine groups,and the frequency of triggered APs and ventricular tachycardia was recorded after the rabbits were given isoprenaline(1 μmol/L) and high-frequency stimulation.RESULTS:The frequency(animals/group) of triggered APs was 0/10 in the sham group,10/10 in the LVH group,4/10 in the KN-93 group,and 1/10 in the ryanodine group.The frequencies of ventricular tachycardia were 0/10,9/10,3/10,and 1/10,respectively.The frequencies of polymorphic ventricular tachycardia or ventricular fibrillation were 0/10,7/10,2/10,and 1/10,respectively.The frequencies of triggered ventricular arrhythmias in the KN-93 and ryanodine groups were much lower than those in the LVH group(P<0.05).CONCLUSIONS:KN-93 and ryanodine can effectively reduce the occurrence of triggered ventricular arrhythmia in rabbits with LVH.The CaMKII-ryanodine signaling pathway can be used as a new means of treating ventricular arrhythmia.展开更多
The insect ryanodine receptor(RyR)is a novel target of the anthranilic and phthalic insecticides,which have high activity against lepidopteran insects.Several diamide insecticides have been used to control pests in or...The insect ryanodine receptor(RyR)is a novel target of the anthranilic and phthalic insecticides,which have high activity against lepidopteran insects.Several diamide insecticides have been used to control pests in orchards in China.To enhance our understanding of the effects of diamides on RyRs,full-length cDNAs were isolated and characterized from the summer fruit tortrix moth,Adoxophyes orana,which is the most severe pest of stone and pome trees worldwide.In addition,the modulation of AoRyRmRNA expression by diamide insecticides was investigated.The AoRyRmRNA obtained had an open reading frame(ORF)of 15402 bp nucleotides encoding 5113 amino acids,and shared high and low identity with its orthologs in other insects and mammals of 77–92 and 45–47%identity,respectively.One alternative splice site with two exclusive exons was revealed in AoRyR(a/b).The usage of exon was more frequent in eggs and larvae than in pupae and adults.Quantitative real-time reverse transcription PCR(qRT-PCR)showed that AoRyRmRNA was expressed at all developmental stages,especially in eggs,male pupae and male adults.The expression levels of AoRyRmRNA in the whole body were up-regulated markedly after 3 rd instar larvae were treated with chlorantraniliprole at LC_(10),LC_(20)and LC_(50)dosages.The results could provide the basis for further functional studies of Ao Ry R and for the development of new chemicals with selective activity against insects.展开更多
基金supported by National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Award Number R01NS092680(to DPS)。
文摘Clinical disability following trauma or disease to the spinal cord often involves the loss of vital white matter elements including axons and glia.Although excessive Cais an established driver of axonal degeneration,therapeutically targeting externally sourced Cato date has had limited success in both basic and clinical studies.Contributing factors that may underlie this limited success include the complexity of the many potential sources of Caentry and the discovery that axons also contain substantial amounts of stored Cathat if inappropriately released could contribute to axonal demise.Axonal Castorage is largely accomplished by the axoplasmic reticulum that is part of a continuous network of the endoplasmic reticulum that provides a major sink and source of intracellular Cafrom the tips of dendrites to axonal terminals.This“neuron-within-a-neuron”is positioned to rapidly respond to diverse external and internal stimuli by amplifying cytosolic Calevels and generating short and long distance regenerative Cawaves through Cainduced Carelease.This review provides a glimpse into the molecular machinery that has been implicated in regulating ryanodine receptor mediated Carelease in axons and how dysregulation and/or overstimulation of these internodal axonal signaling nanocomplexes may directly contribute to Ca-dependent axonal demise.Neuronal ryanodine receptors expressed in dendrites,soma,and axonal terminals have been implicated in synaptic transmission and synaptic plasticity,but a physiological role for internodal localized ryanodine receptors remains largely obscure.Plausible physiological roles for internodal ryanodine receptors and such an elaborate internodal binary membrane signaling network in axons will also be discussed.
基金supported by a grant from Surface Project of Natural Science Foundation of Fujian Province(2008J0075)
文摘BACKGROUND:Calcium calmodulin-dependent kinase II(CaMKII) can be more active in patients with left ventricular hypertrophy(LVH),which in turn causes phosphorylation of ryanodine receptors,resulting in inactivation and the instability of intracellular calcium homeostasis.The present study aimed to determine the effect of CaMKII-ryanodine receptor pathway signaling in rabbits with left ventricular hypertrophy and triggered ventricular arrhythmia.METHODS:Forty New Zealand rabbits were randomized into four groups(10 per group):sham group,LVH group,KN-93 group(LVH+KN-93),and ryanodine group(LVH+ryanodine).Rabbits in the LVH,KN-93,and ryanodine groups were used to establish a left ventricular hypertrophy model by the coarctation of the abdominal aorta,while those in the sham group did not undergo the coarctation.After eight weeks,action potentials(APs) were recorded simultaneously in the endocardium and epicardium,and a transmural electrocardiogram(ECG) was also recorded in the rabbit left ventricular wedge model.Drugs were administered to the animals in the KN-93 and ryanodine groups,and the frequency of triggered APs and ventricular tachycardia was recorded after the rabbits were given isoprenaline(1 μmol/L) and high-frequency stimulation.RESULTS:The frequency(animals/group) of triggered APs was 0/10 in the sham group,10/10 in the LVH group,4/10 in the KN-93 group,and 1/10 in the ryanodine group.The frequencies of ventricular tachycardia were 0/10,9/10,3/10,and 1/10,respectively.The frequencies of polymorphic ventricular tachycardia or ventricular fibrillation were 0/10,7/10,2/10,and 1/10,respectively.The frequencies of triggered ventricular arrhythmias in the KN-93 and ryanodine groups were much lower than those in the LVH group(P<0.05).CONCLUSIONS:KN-93 and ryanodine can effectively reduce the occurrence of triggered ventricular arrhythmia in rabbits with LVH.The CaMKII-ryanodine signaling pathway can be used as a new means of treating ventricular arrhythmia.
基金the National Key R&D Program of China(2017YFD0200300)the Fundamental Research Funds for Central Non-profit Scientific Institution,China(1610182019011)。
文摘The insect ryanodine receptor(RyR)is a novel target of the anthranilic and phthalic insecticides,which have high activity against lepidopteran insects.Several diamide insecticides have been used to control pests in orchards in China.To enhance our understanding of the effects of diamides on RyRs,full-length cDNAs were isolated and characterized from the summer fruit tortrix moth,Adoxophyes orana,which is the most severe pest of stone and pome trees worldwide.In addition,the modulation of AoRyRmRNA expression by diamide insecticides was investigated.The AoRyRmRNA obtained had an open reading frame(ORF)of 15402 bp nucleotides encoding 5113 amino acids,and shared high and low identity with its orthologs in other insects and mammals of 77–92 and 45–47%identity,respectively.One alternative splice site with two exclusive exons was revealed in AoRyR(a/b).The usage of exon was more frequent in eggs and larvae than in pupae and adults.Quantitative real-time reverse transcription PCR(qRT-PCR)showed that AoRyRmRNA was expressed at all developmental stages,especially in eggs,male pupae and male adults.The expression levels of AoRyRmRNA in the whole body were up-regulated markedly after 3 rd instar larvae were treated with chlorantraniliprole at LC_(10),LC_(20)and LC_(50)dosages.The results could provide the basis for further functional studies of Ao Ry R and for the development of new chemicals with selective activity against insects.
