Since the first plant cyclic nucleotide-gated ion channel （CNGC）, HvCBT1, was identified as a calmodulin bind- ing protein, more than a decade has passed and a substantial amount of work has been done to understand ...Since the first plant cyclic nucleotide-gated ion channel （CNGC）, HvCBT1, was identified as a calmodulin bind- ing protein, more than a decade has passed and a substantial amount of work has been done to understand the molecular nature and function of these channel proteins. Based on electrophysiological and heterologous expression analyses, plant CNGCs function as non-selective cation channels and, so far, their biological roles have been reported in defense responses, development, and ion homeostasis. Forward genetic approaches identified four AtCNGCs （AtCNGC2, 4, 11, and 12） to be involved in plant immunity, as null mutants for AtCNGC2, 4, 11, and 12 as well as a gain-of- function mutant for AtCNGC11 and 12 exhibited alterations in defense responses. Since ion flux changes have been reported as one of the early events upon pathogen recognition and also are an essential component for the activation of defense responses, the involvement of CNGCs in these ion flux changes has been suggested. However, the recent detailed characterization of null mutants suggested a more complex involvement of this channel family. In this review, we focus on the discoveries and character- ization of these CNGC mutants and discuss possible roles of CNGCs as components in plant immunity.展开更多
To investigate the mechanisms of microwave induced pacemaker cell injuries, Wistar rats and the primary pacemaker cells of newborn Wistar rats were exposed to microwave at average power density of 50 mW/cm2. Slower sp...To investigate the mechanisms of microwave induced pacemaker cell injuries, Wistar rats and the primary pacemaker cells of newborn Wistar rats were exposed to microwave at average power density of 50 mW/cm2. Slower spontaneous beating rate, intercellular Ca2＋ aggregation and cell membrane perforation were detected immediately after the exposure. Moreover, hyperpolarizationactivated cyclic nucleotide-gated cation channel 4 （HCN4） was down-regulated immediately after the exposure and up-regulated at 12 h after the exposure. In the sinoatrial node （SAN） of the rats,展开更多
Although it has been more than 165 years since the first introduction of modern anesthesia to the clinic, there is surprisingly little understanding about the exact mechanisms by which general anesthetics induce uncon...Although it has been more than 165 years since the first introduction of modern anesthesia to the clinic, there is surprisingly little understanding about the exact mechanisms by which general anesthetics induce unconsciousness. As a result, we do not know how general anesthetics produce anesthesia at different levels. The main handicap to understanding the mechanisms of general anesthesia is the diversity of chemically unrelated compounds including diethyl ether and halogenated hydrocarbons, gases nitrous oxide, ketamine, propofol, benzodiazepines and etomidate, as well as alcohols and barbiturates. Does this imply that general anesthesia is caused by many different mechanisms? Until now, many receptors, molecular targets and neuronal transmission pathways have been shown to contribute to mechanisms of general anesthesia. Among these molecular targets, ion channels are the most likely candidates for general anesthesia, in particular γ-aminobutyric acid type A, potassium and sodium channels, as well as ion channels mediated by various neuronal transmitters like acetylcholine, amino acids amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid or N-methyl-D-aspartate. In addition, recent studies have demonstrated the involvement in general anesthesia of other ion channels with distinct gating properties suchas hyperpolarization-activated, cyclic- nucleotide-gated channels. The main aim of the present review is to summarize some aspects of current knowledge of the effects of general anesthetics on various ion channels.展开更多
Introduction Peptides made up of alternating L- and D- amino acids can form β-helices as in gramicidin A or cyclic peptides that aggregate to form tubes In both cases the structures are hollow with all the side chai...Introduction Peptides made up of alternating L- and D- amino acids can form β-helices as in gramicidin A or cyclic peptides that aggregate to form tubes In both cases the structures are hollow with all the side chains projecting outwards. Kennedy et al. postulated that. peptides having the （LLLD）n configuration could form helices with every fourth side chain projecting inward. It is a fact that synthetic N-formyl- （LeuSerLeuGly） 6- OH, when added to a lipid bilayer, dimerizes, to form ion channels having conductances greater than that of gramicidin.展开更多
Background The cyclic nucleotide-gated channel(CNGC)gene family plays a significant role in the uptake of both essential and toxic cations,and has a role in enhancing tolerance to various forms of abiotic stresses as ...Background The cyclic nucleotide-gated channel(CNGC)gene family plays a significant role in the uptake of both essential and toxic cations,and has a role in enhancing tolerance to various forms of abiotic stresses as well as the modulation of the heavy metal toxicity to plant through the absorption of heavy metals.Results A complete genome-wide identification and functional characterization of the cotton CNGC genes was carried out,in which 55,28,and 29 CNGC genes were identified in Gossypium hirsutum,G.raimondii,and G.arboreum,respectively.The protein encoded by the CNGC genes exhibited GRAVY value below zero,indicating their hydrophilic property.CNGC genes were unevenly distributed in 19 out of 26 chromosomes,in which the highest density were observed on Ah05,with 8 genes.High gene coverage was observed among the diploid cotton species,with CNGC genes mapped on all A chromosomes and on 11 out of 13 of D chromosomes.The majority of CNGC proteins were localized in the endoplasmic reticulum,nucleus,and plasma membrane.Gene expression analysis revealed the up-regulation of Gh_A01G0520(CNGC4)and Gh_D13G1974(CNGC5)across various forms of abiotic stresses.Moreover,down-regulation of Gh_A01G0520(CNGC4)and Gh_D13G1974(CNGC5)in CNGCs silenced plants caused the significantly reduced ability to tolerate drought and salt stresses.All CNGCs silenced plants were recorded to have significantly low content of antioxidants but relatively higher content of oxidant,including MDA and H_(2)O_(2).Furthermore,SPAD,CMS(cell membrane stability),ELWL(excised leaf water loss),SDW(shoot dry matter weight),and RDW(root dry matter weight)were all lower in CNGCs silenced plants compared with the wild type plants.Conclusion Significant reduction in antioxidant content and negative effects of physiological and morphological characters in CNGCs silenced plants has revealed the novel role of CNGC genes in enhancing cell integrity under abiotic stress conditions.These results provide vital information that will expand our understanding of the CNGC gene family in cotton and other plants,thus promoting the integration of these genes in the development of the environmental resilient plants.展开更多
The action potential of pacemaker cells in the sino-atrial node forms the automatic rhythm of the heart. The automatic depolarization in phase 4 is me DaSlS of the automaticity in pacemaker cells. Many currents are in...The action potential of pacemaker cells in the sino-atrial node forms the automatic rhythm of the heart. The automatic depolarization in phase 4 is me DaSlS of the automaticity in pacemaker cells. Many currents are included in phase 4, such as calcium current, TTX-sensitive sodium current, sustained inward current （Isi）, decay of delayed rectifier potassium current, etc. Funny current （If） has long been recognized as important in this phase and is activated at hyperpolarized potentials during cell diastole and in turn activates other currents to form automatic depolarization.展开更多
OBJECTIVE:To explore the mechanisms of dorsal root ganglia and spinal microglia cascade cross in electroacupuncture(EA)analgesia in the treatment of lumbar disc herniation.METHODS:A rat model of lumbar disc herniation...OBJECTIVE:To explore the mechanisms of dorsal root ganglia and spinal microglia cascade cross in electroacupuncture(EA)analgesia in the treatment of lumbar disc herniation.METHODS:A rat model of lumbar disc herniation(LDH)was established,EA was administered at Huantiao(GB30)acupoint 30 min once a day,for 3 d.Before and after modeling,and after EA,mechanical allodynia thresholds were detected.Hyperpolarization-activated cyclic nucleotide-gated 2(HCN2)in dorsal root ganglia was detected by quantitative polymerase chain reaction(qPCR)and Western blot.C-X3-C motif chemokine ligand 1(CX3CL1)and activity of microglia in spinal cord was observed separately via qPCR and immunofluorescence staining.RESULTS:The mechanical allodynia threshold of the right planta of model rats was significantly reduced(P<0.01),EA increased the mechanical pain threshold of rats(P<0.01),and decreased HCN2 mRNA,and protein expression,reduced the expression of CX3CL1 and the activation of microglia.ZD7288(a blocker of HCN channel)reduced the analgesic effect of EA from 1.83±0.84 to 0.74±0.20(P<0.05),and the expression of CX3CL1 in the spinal cord decreased from 0.52±0.11 to 0.15±0.05(P<0.01).CONCLUSION:EA analgesia on the radicular pain of LDH is definite.EA reduced the expression of HCN2 channel in the dorsal root ganglion,thereby decreasing the noxious stimulation entered to microglia in spinal dorsal horn.Our work supports EA is an effective treatment for radicular pain of LDH.展开更多
Complete congenital achromatopsia is a devastating hereditary visual disorder. Mutations in the CNGB3 gene account for more than 50% of all known cases of achromatopsia. This work investigated the efficiency of subret...Complete congenital achromatopsia is a devastating hereditary visual disorder. Mutations in the CNGB3 gene account for more than 50% of all known cases of achromatopsia. This work investigated the efficiency of subretinal(SR) delivered AAV8(Y447, 733 F) vector containing a human PR2.1 promoter and a human CNGB3 c DNA in Cngb3-/-/Nrl-/-mice. The Cngb3-/-/Nrl-/- mouse was a cone-dominant model with Cngb3 channel deficiency, which partially mimicked the all-cone foveal structure of human achromatopsia with CNGB3 mutations. Following SR delivery of the vector, AAV-mediated CNGB3 expression restored cone function which was assessed by the restoration of the cone-mediated electroretinogram(ERG) and immunohistochemistry. This therapeutic rescue resulted in long-term improvement of retinal function with the restoration of cone ERG amplitude. This study demonstrated an AAV-mediated gene therapy in a cone-dominant mouse model using a human gene construct and provided the potential to be utilized in clinical trials.展开更多
环核苷酸门控离子通道（cyclic nucleotide-gated ion channels,CNG）是非选择性的阳离子通道,直接被环核苷酸活化.6个不同基因编码CNG离子通道蛋白,4个A亚单元（A1～A4）和2个B亚单元（B1,B3）.CNG离子通道是由2个或3个不同的亚单元组...环核苷酸门控离子通道（cyclic nucleotide-gated ion channels,CNG）是非选择性的阳离子通道,直接被环核苷酸活化.6个不同基因编码CNG离子通道蛋白,4个A亚单元（A1～A4）和2个B亚单元（B1,B3）.CNG离子通道是由2个或3个不同的亚单元组成的异四聚体复合物,是Ca^2＋进入细胞内的主要通道之一.CNG离子通道的活性可被Ca^2＋/CaM及磷酸化/去磷酸化作用所调节,从而改变细胞内钙离子浓度,触发一系列生理效应.近年来CNG离子通道的研究进展神速,成为生命科学的一个热点领域.本文对CNG离子通道的结构、功能及活性调节机制进行了综述.展开更多
文摘Since the first plant cyclic nucleotide-gated ion channel （CNGC）, HvCBT1, was identified as a calmodulin bind- ing protein, more than a decade has passed and a substantial amount of work has been done to understand the molecular nature and function of these channel proteins. Based on electrophysiological and heterologous expression analyses, plant CNGCs function as non-selective cation channels and, so far, their biological roles have been reported in defense responses, development, and ion homeostasis. Forward genetic approaches identified four AtCNGCs （AtCNGC2, 4, 11, and 12） to be involved in plant immunity, as null mutants for AtCNGC2, 4, 11, and 12 as well as a gain-of- function mutant for AtCNGC11 and 12 exhibited alterations in defense responses. Since ion flux changes have been reported as one of the early events upon pathogen recognition and also are an essential component for the activation of defense responses, the involvement of CNGCs in these ion flux changes has been suggested. However, the recent detailed characterization of null mutants suggested a more complex involvement of this channel family. In this review, we focus on the discoveries and character- ization of these CNGC mutants and discuss possible roles of CNGCs as components in plant immunity.
文摘To investigate the mechanisms of microwave induced pacemaker cell injuries, Wistar rats and the primary pacemaker cells of newborn Wistar rats were exposed to microwave at average power density of 50 mW/cm2. Slower spontaneous beating rate, intercellular Ca2＋ aggregation and cell membrane perforation were detected immediately after the exposure. Moreover, hyperpolarizationactivated cyclic nucleotide-gated cation channel 4 （HCN4） was down-regulated immediately after the exposure and up-regulated at 12 h after the exposure. In the sinoatrial node （SAN） of the rats,
文摘Although it has been more than 165 years since the first introduction of modern anesthesia to the clinic, there is surprisingly little understanding about the exact mechanisms by which general anesthetics induce unconsciousness. As a result, we do not know how general anesthetics produce anesthesia at different levels. The main handicap to understanding the mechanisms of general anesthesia is the diversity of chemically unrelated compounds including diethyl ether and halogenated hydrocarbons, gases nitrous oxide, ketamine, propofol, benzodiazepines and etomidate, as well as alcohols and barbiturates. Does this imply that general anesthesia is caused by many different mechanisms? Until now, many receptors, molecular targets and neuronal transmission pathways have been shown to contribute to mechanisms of general anesthesia. Among these molecular targets, ion channels are the most likely candidates for general anesthesia, in particular γ-aminobutyric acid type A, potassium and sodium channels, as well as ion channels mediated by various neuronal transmitters like acetylcholine, amino acids amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid or N-methyl-D-aspartate. In addition, recent studies have demonstrated the involvement in general anesthesia of other ion channels with distinct gating properties suchas hyperpolarization-activated, cyclic- nucleotide-gated channels. The main aim of the present review is to summarize some aspects of current knowledge of the effects of general anesthetics on various ion channels.
文摘Introduction Peptides made up of alternating L- and D- amino acids can form β-helices as in gramicidin A or cyclic peptides that aggregate to form tubes In both cases the structures are hollow with all the side chains projecting outwards. Kennedy et al. postulated that. peptides having the （LLLD）n configuration could form helices with every fourth side chain projecting inward. It is a fact that synthetic N-formyl- （LeuSerLeuGly） 6- OH, when added to a lipid bilayer, dimerizes, to form ion channels having conductances greater than that of gramicidin.
基金funded by the National Natural Science Foundation of China(31621005,32072023)National Key R&D Program of China(2021YFE0101200)PSF/CRP/18th Protocol(07)。
文摘Background The cyclic nucleotide-gated channel(CNGC)gene family plays a significant role in the uptake of both essential and toxic cations,and has a role in enhancing tolerance to various forms of abiotic stresses as well as the modulation of the heavy metal toxicity to plant through the absorption of heavy metals.Results A complete genome-wide identification and functional characterization of the cotton CNGC genes was carried out,in which 55,28,and 29 CNGC genes were identified in Gossypium hirsutum,G.raimondii,and G.arboreum,respectively.The protein encoded by the CNGC genes exhibited GRAVY value below zero,indicating their hydrophilic property.CNGC genes were unevenly distributed in 19 out of 26 chromosomes,in which the highest density were observed on Ah05,with 8 genes.High gene coverage was observed among the diploid cotton species,with CNGC genes mapped on all A chromosomes and on 11 out of 13 of D chromosomes.The majority of CNGC proteins were localized in the endoplasmic reticulum,nucleus,and plasma membrane.Gene expression analysis revealed the up-regulation of Gh_A01G0520(CNGC4)and Gh_D13G1974(CNGC5)across various forms of abiotic stresses.Moreover,down-regulation of Gh_A01G0520(CNGC4)and Gh_D13G1974(CNGC5)in CNGCs silenced plants caused the significantly reduced ability to tolerate drought and salt stresses.All CNGCs silenced plants were recorded to have significantly low content of antioxidants but relatively higher content of oxidant,including MDA and H_(2)O_(2).Furthermore,SPAD,CMS(cell membrane stability),ELWL(excised leaf water loss),SDW(shoot dry matter weight),and RDW(root dry matter weight)were all lower in CNGCs silenced plants compared with the wild type plants.Conclusion Significant reduction in antioxidant content and negative effects of physiological and morphological characters in CNGCs silenced plants has revealed the novel role of CNGC genes in enhancing cell integrity under abiotic stress conditions.These results provide vital information that will expand our understanding of the CNGC gene family in cotton and other plants,thus promoting the integration of these genes in the development of the environmental resilient plants.
基金This study was supported by the grants from the National"863"Program(No.2001AA2160313)Beijing Important Program Fund of Science and Technology(No.H020220010490)Capital Medical Development Fund of Science and Technology(No.2003-3002)
文摘The action potential of pacemaker cells in the sino-atrial node forms the automatic rhythm of the heart. The automatic depolarization in phase 4 is me DaSlS of the automaticity in pacemaker cells. Many currents are included in phase 4, such as calcium current, TTX-sensitive sodium current, sustained inward current （Isi）, decay of delayed rectifier potassium current, etc. Funny current （If） has long been recognized as important in this phase and is activated at hyperpolarized potentials during cell diastole and in turn activates other currents to form automatic depolarization.
基金Supported by Inheritance and Innovation in TCM“Hundred-Thousand-Ten Thousand”Talent Project(Qinhuang Project)(No.F119090038)the National Natural Science Foundation of China(Based on the Cascade Reaction of Microglia-Astrocyte research exosomal mi RNA mechanisms of the inhibitory transition from acute to chronic pain of LDH by electroacupuncture,No.82074529)Scientific Research Projects of Traditional Chinese Medicine Bureau of Guangdong Province(Based on the cAMP-PKA-HCN2 pathway the mechanism of electro-acupuncture to prevent the development of pain in lumbar disc herniation,No.20211254)
文摘OBJECTIVE:To explore the mechanisms of dorsal root ganglia and spinal microglia cascade cross in electroacupuncture(EA)analgesia in the treatment of lumbar disc herniation.METHODS:A rat model of lumbar disc herniation(LDH)was established,EA was administered at Huantiao(GB30)acupoint 30 min once a day,for 3 d.Before and after modeling,and after EA,mechanical allodynia thresholds were detected.Hyperpolarization-activated cyclic nucleotide-gated 2(HCN2)in dorsal root ganglia was detected by quantitative polymerase chain reaction(qPCR)and Western blot.C-X3-C motif chemokine ligand 1(CX3CL1)and activity of microglia in spinal cord was observed separately via qPCR and immunofluorescence staining.RESULTS:The mechanical allodynia threshold of the right planta of model rats was significantly reduced(P<0.01),EA increased the mechanical pain threshold of rats(P<0.01),and decreased HCN2 mRNA,and protein expression,reduced the expression of CX3CL1 and the activation of microglia.ZD7288(a blocker of HCN channel)reduced the analgesic effect of EA from 1.83±0.84 to 0.74±0.20(P<0.05),and the expression of CX3CL1 in the spinal cord decreased from 0.52±0.11 to 0.15±0.05(P<0.01).CONCLUSION:EA analgesia on the radicular pain of LDH is definite.EA reduced the expression of HCN2 channel in the dorsal root ganglion,thereby decreasing the noxious stimulation entered to microglia in spinal dorsal horn.Our work supports EA is an effective treatment for radicular pain of LDH.
基金supported by NIH(Grant No.EY023543 to J.P.)Jiangsu Province Foundation for Innovative Research Team(to C.Z.).
文摘Complete congenital achromatopsia is a devastating hereditary visual disorder. Mutations in the CNGB3 gene account for more than 50% of all known cases of achromatopsia. This work investigated the efficiency of subretinal(SR) delivered AAV8(Y447, 733 F) vector containing a human PR2.1 promoter and a human CNGB3 c DNA in Cngb3-/-/Nrl-/-mice. The Cngb3-/-/Nrl-/- mouse was a cone-dominant model with Cngb3 channel deficiency, which partially mimicked the all-cone foveal structure of human achromatopsia with CNGB3 mutations. Following SR delivery of the vector, AAV-mediated CNGB3 expression restored cone function which was assessed by the restoration of the cone-mediated electroretinogram(ERG) and immunohistochemistry. This therapeutic rescue resulted in long-term improvement of retinal function with the restoration of cone ERG amplitude. This study demonstrated an AAV-mediated gene therapy in a cone-dominant mouse model using a human gene construct and provided the potential to be utilized in clinical trials.
文摘环核苷酸门控离子通道（cyclic nucleotide-gated ion channels,CNG）是非选择性的阳离子通道,直接被环核苷酸活化.6个不同基因编码CNG离子通道蛋白,4个A亚单元（A1～A4）和2个B亚单元（B1,B3）.CNG离子通道是由2个或3个不同的亚单元组成的异四聚体复合物,是Ca^2＋进入细胞内的主要通道之一.CNG离子通道的活性可被Ca^2＋/CaM及磷酸化/去磷酸化作用所调节,从而改变细胞内钙离子浓度,触发一系列生理效应.近年来CNG离子通道的研究进展神速,成为生命科学的一个热点领域.本文对CNG离子通道的结构、功能及活性调节机制进行了综述.
基金This work was supported by the Provincial Key Projects for Scientifical and Technological Research of Zhejiang Province (No. 2006C12058)National Natural Science Foundation of China (No. 30571335) and a Grant-in-Aid for Innovative Training of Doctoral Students in JIangsu Province,China.
