Activin A, which was first described in 1986, has been shown to maintain hippocampal neuronal survival. Activin A increases intracellular free Ca2＋ via L-type Ca2＋ channels. Our previous study showed that activin A ...Activin A, which was first described in 1986, has been shown to maintain hippocampal neuronal survival. Activin A increases intracellular free Ca2＋ via L-type Ca2＋ channels. Our previous study showed that activin A promotes neurite growth of dorsal root ganglia in embryonic chickens and inhibits nitric oxide secretion. The present study demonstrated for the first time that activin A could maintain cerebral cortex neuronal survival in vitro for a long period, and that activin A was shown to increase voltage-gated Na＋ current （/Na） in Neuro-2a cells, which was recorded by patch clamp technique. The present study revealed a novel mechanism for activin A, as well as the influence of activin A on neurons by regulating expressions of vasoactive intestine peptide and inducible nitric oxide synthase.展开更多
Interleukin-6 has been shown to be involved in nerve injury and nerve regeneration, but the effects of long-term administration of high concentrations of interleukin-6 on neurons in the central nervous system is poorl...Interleukin-6 has been shown to be involved in nerve injury and nerve regeneration, but the effects of long-term administration of high concentrations of interleukin-6 on neurons in the central nervous system is poorly understood. This study investigated the effects of 24 hour expo-sure of interleukin-6 on cortical neurons at various concentrations （0.1, 1, 5 and 10 ng/mL） and the effects of 10 ng/mL interleukin-6 exposure to cortical neurons for various durations （2, 4, 8, 24 and 48 hours） by studying voltage-gated Na＋ channels using a patch-clamp technique. Volt-age-clamp recording results demonstrated that interleukin-6 suppressed Na＋ currents through its receptor in a time- and dose-dependent manner, but did not alter voltage-dependent activation and inactivation. Current-clamp recording results were consistent with voltage-clamp recording results. Interleukin-6 reduced the action potential amplitude of cortical neurons, but did not change the action potential threshold. The regulation of voltage-gated Na＋channels in rat corti-cal neurons by interleukin-6 is time- and dose-dependent.展开更多
Atrial fibrillation(AF)is the most common cardiac arrhythmia worldwide.The prevalence of the disease increases with age,strongly implying an age-related process underlying the pathology.At a time when people are livin...Atrial fibrillation(AF)is the most common cardiac arrhythmia worldwide.The prevalence of the disease increases with age,strongly implying an age-related process underlying the pathology.At a time when people are living longer than ever before,an exponential increase in disease prevalence is predicted worldwide.Hence unraveling the underlying mechanics of the disease is paramount for the development of innovative treatment and prevention strategies.The role of voltage-gated sodium channels is fundamental in cardiac electrophysiology and may provide novel insights into the arrhythmogenesis of AF.Na_v1.5 is the predominant cardiac isoform,responsible for the action potential upstroke.Recent studies have demonstrated that Na_v1.8(an isoform predominantly expressed within the peripheral nervous system)is responsible for cellular arrhythmogenesis through the enhancement of pro-arrhythmogenic currents.Animal studies have shown a decline in Na_v1.5 leading to a diminished action potential upstroke during phase 0.Furthermore,the study of human tissue demonstrates an inverse expression of sodium channel isoforms;reduction of Na_v1.5 and increase of Na_v1.8 in both heart failure and ventricular hypertrophy.This strongly suggests that the expression of voltage-gated sodium channels play a crucial role in the development of arrhythmias in the diseased heart.Targeting aberrant sodium currents has led to novel therapeutic approaches in tackling AF and continues to be an area of emerging research.This review will explore how voltage-gated sodium channels may predispose the elderly heart to AF through the examination of laboratory and clinical based evidence.展开更多
Objective:To investigate the different suppressive effect of lidocaine on persistent Na^+ current and transient Na^+ current in injured or uninjured dorsal root ganglion neurons.Methods:Totally 23 SD rats were randoml...Objective:To investigate the different suppressive effect of lidocaine on persistent Na^+ current and transient Na^+ current in injured or uninjured dorsal root ganglion neurons.Methods:Totally 23 SD rats were randomly divided into 2 groups:control group(n=10) and chronically compressed DRG(dorsal root ganglion) group (CCD group,n=13).Rats were anesthetized and DRG was isolated.Single DRG neuron was isolated by enzymatic disassociation method.Persistent Na^+ current(I_(NaP)) and transient Na^+ current(I_(NaT)) were elicited in voltage clamp mode.Results:The presence of I_(NaP) was testified in most DRG neurons (38/46 neurons in CCD group and 31/39 neurons in control group,P>0.05).However,the cur- rent density of I_(NaP) in CCD group(4.6±0.6 pA/pF,n=38 neurons) was greater than that in control group (2.5±0.4 pA/pF,n=31 neurons)(P<0.05).The characteristics of I_(NaP) was observed and found that I_(NaP) could be blocked by 0.2μmol/L tetrodotoxin easily.Furthermore,the does-effect relationship of lidocaine on I_(NaP) and I_(NaT) were also examined.I_(NaP) and I_(NaT) were suppressed by different concentrations of li- docaine,the range for I_(NaP) was 5-20μmol/L and for I_(NaT) was 0.05-2 mmol/L.Conclusion:I_(NaP) and I_(NaT) were suppressed by different concentrations of iidocaine.I_(NaP) was suppressed by very low concentration of lidocaine(5-20μmol/L).However,I_(NaT) could only be blocked by high concentration of lidocaine(0.05-2 mmol/L).展开更多
To determine the effects of HOE 694, a new and potent Na＋- H＋ exchanger blocker, on transient inward current (Iti) and Na＋- Ca2＋ exchange during hypoxia- reoxygenation in guinea pig cardiomyocytes. Methods. Cardio...To determine the effects of HOE 694, a new and potent Na＋- H＋ exchanger blocker, on transient inward current (Iti) and Na＋- Ca2＋ exchange during hypoxia- reoxygenation in guinea pig cardiomyocytes. Methods. Cardiomyocytes were isolated from adult guinea pig ventricle. Experiment was performed in an experimental chamber that allowed the cells to be exposed to a sufficiently low O2 pressure. The cells were subjected to hypoxia and reoxygenation. The ionic currents were studied with patch clamp technique. Results. In the absence of HOE 694, hypoxia- reoxygenation induced Iti in 12 of 15 experiments; but in cardiomyocytes pretreated with HOE 694 (10～ 50μ mol/L), the incidence of Iti observed during reoxygenation was reduced to 5 of 11 experiments and 3 of 10 experiments, P Conclusions. Blockade of the Na＋- H＋ exchange by HOE 694 could reduce Ca2＋ overload upon hypoxia- reoxygenation, and inhibition of Na＋- H＋ exchange may also indirectly decrease Na＋- Ca2＋ exchange activity during hypoxia.展开更多
Physiotherapeutic effects of infrared lasers have been proved in clinic.These infrared-based regulations of the bioelectrical activities can roughly be classied into enhancement and suppression of action potential(AP)...Physiotherapeutic effects of infrared lasers have been proved in clinic.These infrared-based regulations of the bioelectrical activities can roughly be classied into enhancement and suppression of action potential(AP),which are described by sodium(Na)and potassium(K)transmembrane current equations,named as Hodgkin and Huxley(HH)-model.The enhancement effect is able to evoke or strengthen the AP when infrared light is applied.Its corresponding mechanism is commonly ascribed to the changes of the cell membrane capacitance,which is transiently increased in response to the infrared radiation.The distinctive feature of the suppression effect is to inhibit or reduce the AP by the designed protocols of infrared radiation.However,its mechanism presents more complexity than that in enhancement cases.HH-model describes how the Na current determines the initial phase of AP.So,the enhancement and suppression of AP can be also ascribed to the regulations of the corresponding Na currents.Here,a continuous infrared light at the wavelength of 980 nm(CIS-980)was employed to stimulate a freshly isolated hippocampal neuron in vitro and a suppression effect on the Na currents of the neuron cell was observed.Both Na and K currents,which are named as whole cell currents,were simultaneously recorded with the cell membrane capacitance current by using a patch clamp combined with infrared irradiation.The results demonstrated that the CIS-980 was able to reversibly increase the capacitance currents,completely suppressed Na currents,but little changed K currents,which forms the steady outward whole cell currents and plays a major role on the AP repolarization.A conrmation experiment was designed and carried out by synchronizing tens of milliseconds of infrared stimulation on the same kinds of hippocampal neuron cells.After the blocked K channel,a reduction of Na current amplitude was still recorded.This proved that infrared suppression of Na current was irrelevant to K channel.A membrane capacitance mediation process was preliminarily proposed to explain the Na channel suppression process.展开更多
Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may de...Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may depend on the pathological process and cell types involved.Voltage-gated sodium channels(VGSCs)are essential ion channels for the generation of action potentials in neurons,and are involved in various neuroexcitation-related diseases.However,the effects of TGF-β1 on the functional properties of VGSCs and firing properties in cortical neurons remain unclear.In this study,we investigated the effects of TGF-β1 on VGSC function and firing properties in primary cortical neurons from mice.We found that TGF-β1 increased VGSC current density in a dose-and time-dependent manner,which was attributable to the upregulation of Nav1.3 expression.Increased VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase(PD98059),p38 mitogen-activated protein kinase(SB203580),and Jun NH2-terminal kinase 1/2 inhibitor(SP600125).Interestingly,TGF-β1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical neurons.These findings suggest that TGF-β1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway,which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological conditions.Thus,this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.展开更多
基金the National Natural Science Foundation of China, No.30903123, 30901329the Project of Science and Technology of Jilin Province, No.20090741, 20090185
文摘Activin A, which was first described in 1986, has been shown to maintain hippocampal neuronal survival. Activin A increases intracellular free Ca2＋ via L-type Ca2＋ channels. Our previous study showed that activin A promotes neurite growth of dorsal root ganglia in embryonic chickens and inhibits nitric oxide secretion. The present study demonstrated for the first time that activin A could maintain cerebral cortex neuronal survival in vitro for a long period, and that activin A was shown to increase voltage-gated Na＋ current （/Na） in Neuro-2a cells, which was recorded by patch clamp technique. The present study revealed a novel mechanism for activin A, as well as the influence of activin A on neurons by regulating expressions of vasoactive intestine peptide and inducible nitric oxide synthase.
基金supported by a grant from the National Natural Science Foundation of China,No.30972766,31170852,81001322,81172795,81173048the Specialized Research Fund for the Doctoral Program of Colleges and Universities,No.20094402110004
文摘Interleukin-6 has been shown to be involved in nerve injury and nerve regeneration, but the effects of long-term administration of high concentrations of interleukin-6 on neurons in the central nervous system is poorly understood. This study investigated the effects of 24 hour expo-sure of interleukin-6 on cortical neurons at various concentrations （0.1, 1, 5 and 10 ng/mL） and the effects of 10 ng/mL interleukin-6 exposure to cortical neurons for various durations （2, 4, 8, 24 and 48 hours） by studying voltage-gated Na＋ channels using a patch-clamp technique. Volt-age-clamp recording results demonstrated that interleukin-6 suppressed Na＋ currents through its receptor in a time- and dose-dependent manner, but did not alter voltage-dependent activation and inactivation. Current-clamp recording results were consistent with voltage-clamp recording results. Interleukin-6 reduced the action potential amplitude of cortical neurons, but did not change the action potential threshold. The regulation of voltage-gated Na＋channels in rat corti-cal neurons by interleukin-6 is time- and dose-dependent.
文摘Atrial fibrillation(AF)is the most common cardiac arrhythmia worldwide.The prevalence of the disease increases with age,strongly implying an age-related process underlying the pathology.At a time when people are living longer than ever before,an exponential increase in disease prevalence is predicted worldwide.Hence unraveling the underlying mechanics of the disease is paramount for the development of innovative treatment and prevention strategies.The role of voltage-gated sodium channels is fundamental in cardiac electrophysiology and may provide novel insights into the arrhythmogenesis of AF.Na_v1.5 is the predominant cardiac isoform,responsible for the action potential upstroke.Recent studies have demonstrated that Na_v1.8(an isoform predominantly expressed within the peripheral nervous system)is responsible for cellular arrhythmogenesis through the enhancement of pro-arrhythmogenic currents.Animal studies have shown a decline in Na_v1.5 leading to a diminished action potential upstroke during phase 0.Furthermore,the study of human tissue demonstrates an inverse expression of sodium channel isoforms;reduction of Na_v1.5 and increase of Na_v1.8 in both heart failure and ventricular hypertrophy.This strongly suggests that the expression of voltage-gated sodium channels play a crucial role in the development of arrhythmias in the diseased heart.Targeting aberrant sodium currents has led to novel therapeutic approaches in tackling AF and continues to be an area of emerging research.This review will explore how voltage-gated sodium channels may predispose the elderly heart to AF through the examination of laboratory and clinical based evidence.
基金the National Natural Science Foundation of China(No.30600581)
文摘Objective:To investigate the different suppressive effect of lidocaine on persistent Na^+ current and transient Na^+ current in injured or uninjured dorsal root ganglion neurons.Methods:Totally 23 SD rats were randomly divided into 2 groups:control group(n=10) and chronically compressed DRG(dorsal root ganglion) group (CCD group,n=13).Rats were anesthetized and DRG was isolated.Single DRG neuron was isolated by enzymatic disassociation method.Persistent Na^+ current(I_(NaP)) and transient Na^+ current(I_(NaT)) were elicited in voltage clamp mode.Results:The presence of I_(NaP) was testified in most DRG neurons (38/46 neurons in CCD group and 31/39 neurons in control group,P>0.05).However,the cur- rent density of I_(NaP) in CCD group(4.6±0.6 pA/pF,n=38 neurons) was greater than that in control group (2.5±0.4 pA/pF,n=31 neurons)(P<0.05).The characteristics of I_(NaP) was observed and found that I_(NaP) could be blocked by 0.2μmol/L tetrodotoxin easily.Furthermore,the does-effect relationship of lidocaine on I_(NaP) and I_(NaT) were also examined.I_(NaP) and I_(NaT) were suppressed by different concentrations of li- docaine,the range for I_(NaP) was 5-20μmol/L and for I_(NaT) was 0.05-2 mmol/L.Conclusion:I_(NaP) and I_(NaT) were suppressed by different concentrations of iidocaine.I_(NaP) was suppressed by very low concentration of lidocaine(5-20μmol/L).However,I_(NaT) could only be blocked by high concentration of lidocaine(0.05-2 mmol/L).
基金This work was supported by Leading Specialty Funding of Shanghai, Grant No.94- III- 001.
文摘To determine the effects of HOE 694, a new and potent Na＋- H＋ exchanger blocker, on transient inward current (Iti) and Na＋- Ca2＋ exchange during hypoxia- reoxygenation in guinea pig cardiomyocytes. Methods. Cardiomyocytes were isolated from adult guinea pig ventricle. Experiment was performed in an experimental chamber that allowed the cells to be exposed to a sufficiently low O2 pressure. The cells were subjected to hypoxia and reoxygenation. The ionic currents were studied with patch clamp technique. Results. In the absence of HOE 694, hypoxia- reoxygenation induced Iti in 12 of 15 experiments; but in cardiomyocytes pretreated with HOE 694 (10～ 50μ mol/L), the incidence of Iti observed during reoxygenation was reduced to 5 of 11 experiments and 3 of 10 experiments, P Conclusions. Blockade of the Na＋- H＋ exchange by HOE 694 could reduce Ca2＋ overload upon hypoxia- reoxygenation, and inhibition of Na＋- H＋ exchange may also indirectly decrease Na＋- Ca2＋ exchange activity during hypoxia.
基金This study was financially supported by the National Natural Science Foundation of China(No.31370835)National Science and Technology Major Special Project on new drug innovation(No.2012ZX09503-001-003)funding from the Dalian University of Technology for the corresponding author(No.DUT21YG121).
文摘Physiotherapeutic effects of infrared lasers have been proved in clinic.These infrared-based regulations of the bioelectrical activities can roughly be classied into enhancement and suppression of action potential(AP),which are described by sodium(Na)and potassium(K)transmembrane current equations,named as Hodgkin and Huxley(HH)-model.The enhancement effect is able to evoke or strengthen the AP when infrared light is applied.Its corresponding mechanism is commonly ascribed to the changes of the cell membrane capacitance,which is transiently increased in response to the infrared radiation.The distinctive feature of the suppression effect is to inhibit or reduce the AP by the designed protocols of infrared radiation.However,its mechanism presents more complexity than that in enhancement cases.HH-model describes how the Na current determines the initial phase of AP.So,the enhancement and suppression of AP can be also ascribed to the regulations of the corresponding Na currents.Here,a continuous infrared light at the wavelength of 980 nm(CIS-980)was employed to stimulate a freshly isolated hippocampal neuron in vitro and a suppression effect on the Na currents of the neuron cell was observed.Both Na and K currents,which are named as whole cell currents,were simultaneously recorded with the cell membrane capacitance current by using a patch clamp combined with infrared irradiation.The results demonstrated that the CIS-980 was able to reversibly increase the capacitance currents,completely suppressed Na currents,but little changed K currents,which forms the steady outward whole cell currents and plays a major role on the AP repolarization.A conrmation experiment was designed and carried out by synchronizing tens of milliseconds of infrared stimulation on the same kinds of hippocampal neuron cells.After the blocked K channel,a reduction of Na current amplitude was still recorded.This proved that infrared suppression of Na current was irrelevant to K channel.A membrane capacitance mediation process was preliminarily proposed to explain the Na channel suppression process.
基金supported by the Natural Science Foundation of Guangdong Province,Nos.2019A1515010649(to WC),2022A1515012044(to JS)the China Postdoctoral Science Foundation,No.2018M633091(to JS).
文摘Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may depend on the pathological process and cell types involved.Voltage-gated sodium channels(VGSCs)are essential ion channels for the generation of action potentials in neurons,and are involved in various neuroexcitation-related diseases.However,the effects of TGF-β1 on the functional properties of VGSCs and firing properties in cortical neurons remain unclear.In this study,we investigated the effects of TGF-β1 on VGSC function and firing properties in primary cortical neurons from mice.We found that TGF-β1 increased VGSC current density in a dose-and time-dependent manner,which was attributable to the upregulation of Nav1.3 expression.Increased VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase(PD98059),p38 mitogen-activated protein kinase(SB203580),and Jun NH2-terminal kinase 1/2 inhibitor(SP600125).Interestingly,TGF-β1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical neurons.These findings suggest that TGF-β1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway,which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological conditions.Thus,this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.
