Objective To examine the effect of deglycosylation on gating properties of rNav1.3. Methods rNav1.3 was expressed in Xenopus oocyte, with glycosylation inhibition by using tunicamycin. Two-electrode voltage clamp was ...Objective To examine the effect of deglycosylation on gating properties of rNav1.3. Methods rNav1.3 was expressed in Xenopus oocyte, with glycosylation inhibition by using tunicamycin. Two-electrode voltage clamp was employed to record the whole-cell sodium current and data were analyzed by Origin software. Those of glycosylated rNav1.3 were kept as control. Results Compared with glycosylated ones, the steady-state activation curve of deglycosylated rNav1.3 was positively shifted by about 10 mV, while inactivation curve was negatively shifted by about 8 mV. Conclusion Glycosylation altered the gating properties of rNav 1.3 and contributed to the functional diversity.展开更多
Voltage-gated sodium channels (VGSCs) play a fundamental role in controlling cellular excitability,and their abnormal activity is related to several pathological processes,including cardiac arrhythmias,epilepsy,neurod...Voltage-gated sodium channels (VGSCs) play a fundamental role in controlling cellular excitability,and their abnormal activity is related to several pathological processes,including cardiac arrhythmias,epilepsy,neurodegenerative diseases,spasticity and chronic pain.In particular,chronic visceral pain,the central symptom of functional gastrointestinal disorders such as irritable bowel syndrome,is a serious clinical problem that affects a high percentage of the world population.In spite of intense research efforts and after the dedicated decade of pain control and research,there are not many options to treat chronic pain conditions.However,there is a wealth of evidence emerging to give hope that a more refined approach may be achievable.By using electronic databases,available data on structural and functional properties of VGSCs in chronic pain,particularly functional gastrointestinal hypersensitivity,were reviewed.We summarize the involvement and molecular bases of action of VGSCs in the pathophysiology of several organic and functionalgastrointestinal disorders.We also describe the efficacy of VGSC blockers in the treatment of these neurological diseases,and outline future developments that may extend the therapeutic use of compounds that target VGSCs.Overall,clinical and experimental data indicate that isoform-specific blockers of these channels or targeting of their modulators may provide effective and novel approaches for visceral pain therapy.展开更多
A new type of piezoelectric electro-hydraulic servo valve system was proposed. And then multilayer piezoelectric actuator based on new piezoelectric ceramic material was used as the electricity-machine converter of th...A new type of piezoelectric electro-hydraulic servo valve system was proposed. And then multilayer piezoelectric actuator based on new piezoelectric ceramic material was used as the electricity-machine converter of the proposed piezoelectric electro-hydraulic servo valve. The proposed piezoelectric electro-hydraulic servo valve has ascendant performance compared with conventional ones. But the system is of high nonlinearity and uncertainty, it cannot achieve favorable control performance by conventional control method. To develop an efficient way to control piezoelectric electro-hydraulic servo valve system, a high-precise fuzzy control method with hysteresis nonlinear model in feedforward loop was proposed. The control method is separated into two parts: a feedforward loop with Preisach hysteresis nonlinear model and a feedback loop with high-precise fuzzy control. Experimental results show that the hysteresis loop and the maximum output hysteresis by the PID control method are 4.22% and 2.11 μm, respectively; the hysteresis loop and the maximum output hysteresis by the proposed control method respectively are 0.74% and 0.37 μm, respectively; the maximum tracking error by the PID control method for sine wave reference signal is about 5.02%, the maximum tracking error by the proposed control method for sine wave reference signal is about 0.85%.展开更多
Objective The purpose of our study is to observe the voltage-gated potassium channel Kvl.3 expressed on CD4＋CD28~ T cells from the peripheral blood of acute coronary syndrome （ACS） patients by the patch clamp techn...Objective The purpose of our study is to observe the voltage-gated potassium channel Kvl.3 expressed on CD4＋CD28~ T cells from the peripheral blood of acute coronary syndrome （ACS） patients by the patch clamp technique. Methods Kvl.3 potassium channels expression from 17 patients with ACS and 11 healthy age-match controls was detected in single cell（CD4＋CD28null T cells and CD4＋CD28＋T cells） by fluorescence mieroscopy and patch clamp. Results The percentage of CD4＋CD28mullT cells was higher in the ACS patients [（6.97±2.05）%] than that in the controls [（1.38±0.84）%, P〈0.05]. The concentration of hsCRP was directly correlated with the number of the CD4~CD28nul~ T cells in the ACS patients （r=0.52, P〈0,05）. The conductance （6.89±1.17ns vs 3.36±0.66ns）, dens （1.95±0.80 μm2 vs 1.13±0.57 μm2） and numbers （574.5±97.6 n/cell vs. 280.3±55.3 n/cell） of the Kv1.3 channels on the CIM＋CD28null T cells were significantly higher than those on the CD4＋CD28＋ T cells （all P〈0.01） in ACS patients, but were similar on CD4＋CD28＋T betweenACS patients and controls. Conclusion The CD4＋CD28nullT cells and the numbers of Kvl.3 channels on the CD4＋CD28nullT cells from patients with ACS are significantly upregulated and might contribute to the pathogenesis of ACS （d Geriatr Cardio12010; 7：40-46）.展开更多
Gold nanoparticles(GNPs)have been extensively used in nanomedicine and neuroscience owing to their biological inertness,peculiar opto-electronic and physico-chemical features.However,the effect of GNPs shape on the ne...Gold nanoparticles(GNPs)have been extensively used in nanomedicine and neuroscience owing to their biological inertness,peculiar opto-electronic and physico-chemical features.However,the effect of GNPs shape on the neurophysiological properties of single neuron is still unclear.To tackle this issue,different shape GNPs(nanosphere,nanotriakisoctahedron and nanoflower)were synthesized to investigate the effect of GNPs on the voltage-dependent sodium channel and the action potential(AP)of hippocampal CA1 neurons in mice.The results indicated that GNPs inhibited the amplitudes of voltage-gated sodium current(I_(Na))and led to a hyperpolarizing shift in the voltage-dependence curve of both activation and inactivation of I_(Na).GNPs also increased neuronal excitability and altered some properties of AP.Moreover,most alterations in AP properties were observed in nanoflower GNPs treated CA1 neurons,suggesting that the neurotoxicity of gold nanoparticles is surface roughness-dependent.These results may provide a valuable direction in the clinical application of GNPs.展开更多
Voltage-gated ion channels(VGICs) are central to cellular excitation, orchestrating skeletal and cardiac muscle contractions and enabling neural signal transduction. Among these, voltage-gated potassium(Kv) channels a...Voltage-gated ion channels(VGICs) are central to cellular excitation, orchestrating skeletal and cardiac muscle contractions and enabling neural signal transduction. Among these, voltage-gated potassium(Kv) channels are particularly significant in cardiac electrophysiology, especially during the repolarization phase of the cardiac action potential. In cardiac myocytes, Kv channels are integral to a multitude of sophisticated functions, including electrical conduction. Despite their importance, research on Kv channels in the context of cardiovascular diseases is limited. This review offers a comprehensive summary of the structural complexities of Kv channels, delineating the regulatory mechanisms involved in channel gating, expression, and membrane localization. Additionally, we examine the role of different Kv α-subunits in modulating Kv channels and their impact on cardiac remodeling, and assess the potential of targeting Kv channels for the development of anti-arrhythmic therapies.展开更多
OBJECTIVE: To examine the effect of electroacupuncture(EA) at bilateral Neiguan(PC 6) on voltage-gated Na+currents(INa) and channels(Nav) in ischemic ventricular myocytes.METHODS: EA serum was prepared from six male a...OBJECTIVE: To examine the effect of electroacupuncture(EA) at bilateral Neiguan(PC 6) on voltage-gated Na+currents(INa) and channels(Nav) in ischemic ventricular myocytes.METHODS: EA serum was prepared from six male adult Sprague-Dawley rats that had received EA at bilateral Neiguan(PC 6). Eighteen ventricular myocytes were prepared from six SD rats using an enzymolysis approach. Myocardial ischemia was mimicked by perfusion of ischemic solution. Whole-cell patch-clamping was used to record three currents evoked from isolated cells. The first current was the control, and recorded in absence of ischemic solution current. The second was the ischemic current,and recorded after perfusion of ischemic solution for 5 min, while the EA current was last, and recorded after perfusion of EA serum for 5 min. Navkinetic curves were fitted using related formulas.RESULTS: Compared with those in controls, in the presence of ischemic solution, peak amplitudes of INasignificantly increased from ﹣40 m V to +30 m V,and half-maximal inactivation potentials of Navincreased significantly, while half-maximal activation potentials, slope factors and the recovery time from inactivation to activation of Navwere unchanged. Compared with those in the ischemic solution, in the presence of EA serum, peak ischemic current amplitudes significantly reduced from ﹣40m V to + 40 m V, and half-maximal inactivation potentials were restored, while half-maximal activation potentials, slope factors and the recovery time from inactivation to activation of Navwere unchanged.CONCLUSION: EA at bilateral Neiguan(PC 6) can reduce enhanced INavia restoration of delayed Navinactivation in ischemic ventricular myocytes.展开更多
Voltage-gated calcium channels(VGCCs) play critical roles in cardiac and skeletal muscle contractions,hormone and neurotransmitter release,as well as slower processes such as cell proliferation,differentiation,migrati...Voltage-gated calcium channels(VGCCs) play critical roles in cardiac and skeletal muscle contractions,hormone and neurotransmitter release,as well as slower processes such as cell proliferation,differentiation,migration and death.Mutations in VGCCs lead to numerous cardiac,muscle and neurological disease,and their physiological function is tightly regulated by kinases,phosphatases,G-proteins,calmodulin and many other proteins.Fifteen years ago,RGK proteins were discovered as the most potent endogenous regulators of VGCCs.They are a family of monomeric GTPases(Rad,Rem,Rem2,and Gem/Kir),in the superfamily of Ras GTPases,and they have two known functions: regulation of cytoskeletal dynamics including dendritic arborization and inhibition of VGCCs.Here we review the mechanisms and molecular determinants of RGK-mediated VGCC inhibition,the physiological impact of this inhibition,and recent evidence linking the two known RGK functions.展开更多
We apply polyelectrolyte multilayer films by consecutive alternate adsorption of positively charged polyallylamine hydrochloride and negatively charged sodium polystyrene sulfonate to the surface of graphene field eff...We apply polyelectrolyte multilayer films by consecutive alternate adsorption of positively charged polyallylamine hydrochloride and negatively charged sodium polystyrene sulfonate to the surface of graphene field effect transistors. Oscillations in the Dirac voltage shift with alternating positive and negative layers clearly demonstrate the electrostatic gating effect in this simple model system. A simple electrostatic model accounts well for the sign and magnitude of the Dirac voltage shift. Using this system, we are able to create p-type or n-type graphene at will. This model serves as the basis for understanding the mechanism of charged polymer sensing using graphene devices, a potentially technologically important application of graphene in areas such as DNA sequencing, biomarker assays for cancer detection, and other protein sensing applications.展开更多
基金the National Basic Research Development Program of China (No. 2006CB500801).
文摘Objective To examine the effect of deglycosylation on gating properties of rNav1.3. Methods rNav1.3 was expressed in Xenopus oocyte, with glycosylation inhibition by using tunicamycin. Two-electrode voltage clamp was employed to record the whole-cell sodium current and data were analyzed by Origin software. Those of glycosylated rNav1.3 were kept as control. Results Compared with glycosylated ones, the steady-state activation curve of deglycosylated rNav1.3 was positively shifted by about 10 mV, while inactivation curve was negatively shifted by about 8 mV. Conclusion Glycosylation altered the gating properties of rNav 1.3 and contributed to the functional diversity.
文摘Voltage-gated sodium channels (VGSCs) play a fundamental role in controlling cellular excitability,and their abnormal activity is related to several pathological processes,including cardiac arrhythmias,epilepsy,neurodegenerative diseases,spasticity and chronic pain.In particular,chronic visceral pain,the central symptom of functional gastrointestinal disorders such as irritable bowel syndrome,is a serious clinical problem that affects a high percentage of the world population.In spite of intense research efforts and after the dedicated decade of pain control and research,there are not many options to treat chronic pain conditions.However,there is a wealth of evidence emerging to give hope that a more refined approach may be achievable.By using electronic databases,available data on structural and functional properties of VGSCs in chronic pain,particularly functional gastrointestinal hypersensitivity,were reviewed.We summarize the involvement and molecular bases of action of VGSCs in the pathophysiology of several organic and functionalgastrointestinal disorders.We also describe the efficacy of VGSC blockers in the treatment of these neurological diseases,and outline future developments that may extend the therapeutic use of compounds that target VGSCs.Overall,clinical and experimental data indicate that isoform-specific blockers of these channels or targeting of their modulators may provide effective and novel approaches for visceral pain therapy.
基金Project(2001AA423270) supported by the National High-Tech Research and Development Program of ChinaProject (2005037185) supported by the Postdoctoral Science Foundation of China
文摘A new type of piezoelectric electro-hydraulic servo valve system was proposed. And then multilayer piezoelectric actuator based on new piezoelectric ceramic material was used as the electricity-machine converter of the proposed piezoelectric electro-hydraulic servo valve. The proposed piezoelectric electro-hydraulic servo valve has ascendant performance compared with conventional ones. But the system is of high nonlinearity and uncertainty, it cannot achieve favorable control performance by conventional control method. To develop an efficient way to control piezoelectric electro-hydraulic servo valve system, a high-precise fuzzy control method with hysteresis nonlinear model in feedforward loop was proposed. The control method is separated into two parts: a feedforward loop with Preisach hysteresis nonlinear model and a feedback loop with high-precise fuzzy control. Experimental results show that the hysteresis loop and the maximum output hysteresis by the PID control method are 4.22% and 2.11 μm, respectively; the hysteresis loop and the maximum output hysteresis by the proposed control method respectively are 0.74% and 0.37 μm, respectively; the maximum tracking error by the PID control method for sine wave reference signal is about 5.02%, the maximum tracking error by the proposed control method for sine wave reference signal is about 0.85%.
文摘Objective The purpose of our study is to observe the voltage-gated potassium channel Kvl.3 expressed on CD4＋CD28~ T cells from the peripheral blood of acute coronary syndrome （ACS） patients by the patch clamp technique. Methods Kvl.3 potassium channels expression from 17 patients with ACS and 11 healthy age-match controls was detected in single cell（CD4＋CD28null T cells and CD4＋CD28＋T cells） by fluorescence mieroscopy and patch clamp. Results The percentage of CD4＋CD28mullT cells was higher in the ACS patients [（6.97±2.05）%] than that in the controls [（1.38±0.84）%, P〈0.05]. The concentration of hsCRP was directly correlated with the number of the CD4~CD28nul~ T cells in the ACS patients （r=0.52, P〈0,05）. The conductance （6.89±1.17ns vs 3.36±0.66ns）, dens （1.95±0.80 μm2 vs 1.13±0.57 μm2） and numbers （574.5±97.6 n/cell vs. 280.3±55.3 n/cell） of the Kv1.3 channels on the CIM＋CD28null T cells were significantly higher than those on the CD4＋CD28＋ T cells （all P〈0.01） in ACS patients, but were similar on CD4＋CD28＋T betweenACS patients and controls. Conclusion The CD4＋CD28nullT cells and the numbers of Kvl.3 channels on the CD4＋CD28nullT cells from patients with ACS are significantly upregulated and might contribute to the pathogenesis of ACS （d Geriatr Cardio12010; 7：40-46）.
基金Project(LY19C090004)supported by the Natural Science Foundation of Zhejiang Province,ChinaProjects(BK20200710,BK2018077)supported by the Natural Science Foundation of Jiangsu Province,China+1 种基金Project(NHKY-2019-19)supported by the Nanjing Polytechnic Institute Start Fund,ChinaProject(202012920026Y)supported by the Innovation and Entrepreneurship Training Program of Jiangsu Province College Students,China。
文摘Gold nanoparticles(GNPs)have been extensively used in nanomedicine and neuroscience owing to their biological inertness,peculiar opto-electronic and physico-chemical features.However,the effect of GNPs shape on the neurophysiological properties of single neuron is still unclear.To tackle this issue,different shape GNPs(nanosphere,nanotriakisoctahedron and nanoflower)were synthesized to investigate the effect of GNPs on the voltage-dependent sodium channel and the action potential(AP)of hippocampal CA1 neurons in mice.The results indicated that GNPs inhibited the amplitudes of voltage-gated sodium current(I_(Na))and led to a hyperpolarizing shift in the voltage-dependence curve of both activation and inactivation of I_(Na).GNPs also increased neuronal excitability and altered some properties of AP.Moreover,most alterations in AP properties were observed in nanoflower GNPs treated CA1 neurons,suggesting that the neurotoxicity of gold nanoparticles is surface roughness-dependent.These results may provide a valuable direction in the clinical application of GNPs.
文摘Voltage-gated ion channels(VGICs) are central to cellular excitation, orchestrating skeletal and cardiac muscle contractions and enabling neural signal transduction. Among these, voltage-gated potassium(Kv) channels are particularly significant in cardiac electrophysiology, especially during the repolarization phase of the cardiac action potential. In cardiac myocytes, Kv channels are integral to a multitude of sophisticated functions, including electrical conduction. Despite their importance, research on Kv channels in the context of cardiovascular diseases is limited. This review offers a comprehensive summary of the structural complexities of Kv channels, delineating the regulatory mechanisms involved in channel gating, expression, and membrane localization. Additionally, we examine the role of different Kv α-subunits in modulating Kv channels and their impact on cardiac remodeling, and assess the potential of targeting Kv channels for the development of anti-arrhythmic therapies.
基金National Essence Basic Research and Development 973 Program:the Effects of Meridian Specific Target Organ Response on Biological Basic Research(No.2012CB518503)
文摘OBJECTIVE: To examine the effect of electroacupuncture(EA) at bilateral Neiguan(PC 6) on voltage-gated Na+currents(INa) and channels(Nav) in ischemic ventricular myocytes.METHODS: EA serum was prepared from six male adult Sprague-Dawley rats that had received EA at bilateral Neiguan(PC 6). Eighteen ventricular myocytes were prepared from six SD rats using an enzymolysis approach. Myocardial ischemia was mimicked by perfusion of ischemic solution. Whole-cell patch-clamping was used to record three currents evoked from isolated cells. The first current was the control, and recorded in absence of ischemic solution current. The second was the ischemic current,and recorded after perfusion of ischemic solution for 5 min, while the EA current was last, and recorded after perfusion of EA serum for 5 min. Navkinetic curves were fitted using related formulas.RESULTS: Compared with those in controls, in the presence of ischemic solution, peak amplitudes of INasignificantly increased from ﹣40 m V to +30 m V,and half-maximal inactivation potentials of Navincreased significantly, while half-maximal activation potentials, slope factors and the recovery time from inactivation to activation of Navwere unchanged. Compared with those in the ischemic solution, in the presence of EA serum, peak ischemic current amplitudes significantly reduced from ﹣40m V to + 40 m V, and half-maximal inactivation potentials were restored, while half-maximal activation potentials, slope factors and the recovery time from inactivation to activation of Navwere unchanged.CONCLUSION: EA at bilateral Neiguan(PC 6) can reduce enhanced INavia restoration of delayed Navinactivation in ischemic ventricular myocytes.
基金supported by the Dyson College 2014 Faculty Summer Research Grant Program (Zafir Buraei)Dyson College 2014 Summer Undergraduate Student-Faculty Research Award (Zafir Buraei and Sukhjinder Kaur)+2 种基金the National Key Basic Research Program of China (2014CB910301 to Yang Jian)the Top Talents Program of Yunnan Province, China (Yang Jian)the US National Institutes of Health (NS053494 to Yang Jian)
文摘Voltage-gated calcium channels(VGCCs) play critical roles in cardiac and skeletal muscle contractions,hormone and neurotransmitter release,as well as slower processes such as cell proliferation,differentiation,migration and death.Mutations in VGCCs lead to numerous cardiac,muscle and neurological disease,and their physiological function is tightly regulated by kinases,phosphatases,G-proteins,calmodulin and many other proteins.Fifteen years ago,RGK proteins were discovered as the most potent endogenous regulators of VGCCs.They are a family of monomeric GTPases(Rad,Rem,Rem2,and Gem/Kir),in the superfamily of Ras GTPases,and they have two known functions: regulation of cytoskeletal dynamics including dendritic arborization and inhibition of VGCCs.Here we review the mechanisms and molecular determinants of RGK-mediated VGCC inhibition,the physiological impact of this inhibition,and recent evidence linking the two known RGK functions.
文摘We apply polyelectrolyte multilayer films by consecutive alternate adsorption of positively charged polyallylamine hydrochloride and negatively charged sodium polystyrene sulfonate to the surface of graphene field effect transistors. Oscillations in the Dirac voltage shift with alternating positive and negative layers clearly demonstrate the electrostatic gating effect in this simple model system. A simple electrostatic model accounts well for the sign and magnitude of the Dirac voltage shift. Using this system, we are able to create p-type or n-type graphene at will. This model serves as the basis for understanding the mechanism of charged polymer sensing using graphene devices, a potentially technologically important application of graphene in areas such as DNA sequencing, biomarker assays for cancer detection, and other protein sensing applications.
