The whole-cell patch-clamp technique was employed to obtain information about the voltage-dependence and kinetics of interaction of 7-chlor-benzylte-trahydropalmatine (7-Cl-BTHP) with cardiac sodium channels. 7-Cl-BTH...The whole-cell patch-clamp technique was employed to obtain information about the voltage-dependence and kinetics of interaction of 7-chlor-benzylte-trahydropalmatine (7-Cl-BTHP) with cardiac sodium channels. 7-Cl-BTHP (30 mol/L) significantly decreased the peak sodium current (from 7. 8±1. 8 nA to 5. 3±1. 4 nA, P<0. 01, n=5), without producing a shift of the current-voltage curve. It shifted the inactivation curves of sodium current to hyperpolarized potentials, and the V(0.5) was shifted from - (82. 5±2. 5) mV to - (95±2.4) mV (P <0. 05, n=4). 7-Cl-BTHP produced a significant use-dependent effect that was proportional to the duration of the voltage step. In addition, 7-Cl-BTHP slowed the recovery of sodium channel from inactivation, which could explain its use-dependent effects on sodium current. The characteristics of 7-Cl-BTHP blockage suggest that this agent binds preferentially to inactivated sodium channels.展开更多
Along with the development of economy and society, type 2 diabetic mellitus(T2DM) has become one of the most common diseases at the global level. As one of the complications of T2 DM, diabetic neuropathic pain(DNP) st...Along with the development of economy and society, type 2 diabetic mellitus(T2DM) has become one of the most common diseases at the global level. As one of the complications of T2 DM, diabetic neuropathic pain(DNP) stubbornly and chronically affects the health and life of human beings. In the pain field, dorsal root ganglion(DRG) is generally considered as the first stage of the sensory pathway where the hyperexcitability of injured neurons is associated with different kinds of peripheral neuropathic pains. The abnormal electrophysiology is mainly due to the changed properties of voltage-gated sodium channels(VGSCs) and the increased sodium currents(INa). Curcumin is an active ingredient extracted from turmeric and has been demonstrated to ameliorate T2 DM and its various complications including DNP effectively. The present study demonstrates that the INa of small-sized DRG neurons are significantly increased with the abnormal electrophysiological characteristics of VGSCs in type 2 diabetic neuropathic pain rats. And these abnormalities can be ameliorated efficaciously by a period of treatment with curcumin.展开更多
The present study was designed to determine the effects of Guanfu base A(GFA) on the late sodium current(INa.L),transient sodium current(INa.T),HERG current(IHERG),and Kv1.5 current(IKv1.5).The values of INa.L,INa.T,I...The present study was designed to determine the effects of Guanfu base A(GFA) on the late sodium current(INa.L),transient sodium current(INa.T),HERG current(IHERG),and Kv1.5 current(IKv1.5).The values of INa.L,INa.T,IHERG and IKv1.5 were recorded using the whole-cell patch clamp technique.Compared with other channels,GFA showed selective blocking activity in late sodium channel.It inhibited INa.L in a concentration-dependent manner with an IC50 of(1.57 ± 0.14) μmol·L-1,which was significantly lower than its IC50 values of(21.17 ± 4.51) μmol·L-1 for the INa.T.The inhibitory effect of GFA on INa,L was not affected by 200μmol·L-1 H2O2.It inhibited IHERG with an IC50 of(273 ± 34) μmol·L-1 and has slight blocking effect on IKv1.5,decreasing IKv1.5 by only 20.6% at 200 μmol·L-1.In summary,GFA inhibited INa.L selectively and remained similar inhibition in presence of reactive oxygen species..These findings may suggest a novel molecular mechanism for the potential clinical application of GFA in the treatment of cardiovascular disorders.展开更多
Utilizing the technique of electrolysis with reverse current,sodium tungsten bronze (Na_xWO_3) crystals were prepared from a molten mixture of sodium tungstate (Na_2WO_4 ) and tungstic trioxide (WO_3) at 800℃. Crys...Utilizing the technique of electrolysis with reverse current,sodium tungsten bronze (Na_xWO_3) crystals were prepared from a molten mixture of sodium tungstate (Na_2WO_4 ) and tungstic trioxide (WO_3) at 800℃. Crystal structure, lattice parameter, and s展开更多
Objective:To study the effects of sodium ferulate on the ultrarapid delayed rectifier K+ current(IKur) in human atrial myocytes. Methods:Human atrial myocytes were isolated by enzyme dispersion method. IKur in human a...Objective:To study the effects of sodium ferulate on the ultrarapid delayed rectifier K+ current(IKur) in human atrial myocytes. Methods:Human atrial myocytes were isolated by enzyme dispersion method. IKur in human atrial myocytes were recorded by using the whole cell patch clamp. The changes of IKur were compared in the absence and the presence of sodium ferulate. Results:There was no effect of 0.4 g/L sodium ferulate on I-V relation of IKur. However, 0.4 g/L sodium ferulate inhibited IKur to some degrees at each test pulse. The current densities of IKur at +60 mV decreased from 4.997 ± 0.35 PA/PF to 3.331 ± 0.26 PA/PF(n = 6, P < 0.05). The inhibitory effect was concentration-dependent. IC50 was(0.41±0.03)g/L and the Hill coefficient was 0.95±0.05. Conclusion:Sodium ferulate as a potassium channel blocker can inhibit IKur in human atrial myocytes effectively.展开更多
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 promot...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(INa) 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
Neuropathic pain has been hypothesized to be the result of aberrant expression and function of sodium channels at the site of injury. To investigate the effects of NaV1.8 antisense oligonucleotide on the expression of...Neuropathic pain has been hypothesized to be the result of aberrant expression and function of sodium channels at the site of injury. To investigate the effects of NaV1.8 antisense oligonucleotide on the expression of sodium channel mRNA in dorsal root ganglion (DRG) neurons in chronic neuropathic pain. 24 Sprague-Dawley rats weighing 200-260 g were anesthetized with the intraperitoneal injection of 300 mg·kg -1 choral hydrate. The CCI model was made by loose ligation of sciatic nerve trunk by 4-0 chromic gut. The mechanical and thermal pain threshold were measured before operation and 1, 3, 5, 7, 9, 11, 13 days after operation. A PE-10 catheter was implanted in subarachnoid space at lumbar region. On the 7th postoperative day the animals were randomly divided into 4 groups. The drugs were injected intrathecally twice a day for 5 consecutive days in group 2-4. The animals were decapitated 14 days after the surgery. The L4-L6 DRG of the operated side was removed and crushed, and total RNA was extracted with Trizol reagent. The contralateral side was used as control. The change of NaV1.8 sodium channel transcripts was determined by RT-PCR. Pain threshold was significantly lowered after CCI as compared with that in control group and was elevated 3 days after antisense oligonucleotide injection. Sensory neuron specific TTX-R sodium channel NaV1.8 transcript was down-regulated after antisense oligonucleotide injection at the dosage of 45 μg as compared with that in CCI group (P<0.01), and it was even greater at the dosage of 90 μg. The intrathecally injected NaV1.8 antisense oligonucleotide can reduce the mechanical allodynia and thermal hyperalgesia partially by downregulating the SNS transcript expression.展开更多
文摘The whole-cell patch-clamp technique was employed to obtain information about the voltage-dependence and kinetics of interaction of 7-chlor-benzylte-trahydropalmatine (7-Cl-BTHP) with cardiac sodium channels. 7-Cl-BTHP (30 mol/L) significantly decreased the peak sodium current (from 7. 8±1. 8 nA to 5. 3±1. 4 nA, P<0. 01, n=5), without producing a shift of the current-voltage curve. It shifted the inactivation curves of sodium current to hyperpolarized potentials, and the V(0.5) was shifted from - (82. 5±2. 5) mV to - (95±2.4) mV (P <0. 05, n=4). 7-Cl-BTHP produced a significant use-dependent effect that was proportional to the duration of the voltage step. In addition, 7-Cl-BTHP slowed the recovery of sodium channel from inactivation, which could explain its use-dependent effects on sodium current. The characteristics of 7-Cl-BTHP blockage suggest that this agent binds preferentially to inactivated sodium channels.
基金This work was supported by the grant from the National Natural Science Foundation of China (grant number. No: 81030002,81170177, 81100215, 81373835).
基金supported by a grant from the National Natural Science Foundation of China(No.81073125)Natural Science Foundation of Zhejiang Province(Y2090252)
文摘Along with the development of economy and society, type 2 diabetic mellitus(T2DM) has become one of the most common diseases at the global level. As one of the complications of T2 DM, diabetic neuropathic pain(DNP) stubbornly and chronically affects the health and life of human beings. In the pain field, dorsal root ganglion(DRG) is generally considered as the first stage of the sensory pathway where the hyperexcitability of injured neurons is associated with different kinds of peripheral neuropathic pains. The abnormal electrophysiology is mainly due to the changed properties of voltage-gated sodium channels(VGSCs) and the increased sodium currents(INa). Curcumin is an active ingredient extracted from turmeric and has been demonstrated to ameliorate T2 DM and its various complications including DNP effectively. The present study demonstrates that the INa of small-sized DRG neurons are significantly increased with the abnormal electrophysiological characteristics of VGSCs in type 2 diabetic neuropathic pain rats. And these abnormalities can be ameliorated efficaciously by a period of treatment with curcumin.
基金supported by the Fundamental Research Funds for the Central Universities(No.JKZ2011007)the National "Key Program for New Drug Research Development"(No.2009 ZX09103-345)
文摘The present study was designed to determine the effects of Guanfu base A(GFA) on the late sodium current(INa.L),transient sodium current(INa.T),HERG current(IHERG),and Kv1.5 current(IKv1.5).The values of INa.L,INa.T,IHERG and IKv1.5 were recorded using the whole-cell patch clamp technique.Compared with other channels,GFA showed selective blocking activity in late sodium channel.It inhibited INa.L in a concentration-dependent manner with an IC50 of(1.57 ± 0.14) μmol·L-1,which was significantly lower than its IC50 values of(21.17 ± 4.51) μmol·L-1 for the INa.T.The inhibitory effect of GFA on INa,L was not affected by 200μmol·L-1 H2O2.It inhibited IHERG with an IC50 of(273 ± 34) μmol·L-1 and has slight blocking effect on IKv1.5,decreasing IKv1.5 by only 20.6% at 200 μmol·L-1.In summary,GFA inhibited INa.L selectively and remained similar inhibition in presence of reactive oxygen species..These findings may suggest a novel molecular mechanism for the potential clinical application of GFA in the treatment of cardiovascular disorders.
基金This study was supported by the National Natural Science Foundation of China (No. 30070307) and the National Special Fund for Doctoral Education & Research Program, Ministry of Education, China (No. 20030698009).
文摘很少研究探索了的背景过渡 cardiomyocytes.This 学习的里面的钠水流( INa )动力学试图探索过渡 cardiomyocytes 类型和 .Methods 的动力学整个房间的补丁夹钳技术被用来在兔子 hearts.Results 的 Koch 三角学习孤立的过渡 cardiomyocytes 的快速的 INa 最大的振幅和密度在类型的 INa 一种and 类型是(-1627?敤楲敶?牦浯琠敨瀠牥灩敨慲???慷?獡慳敹?祢洠硩摥氠略潫祣整爠慥瑣潩??剌?整瑳?慌瑣瑡?
文摘Utilizing the technique of electrolysis with reverse current,sodium tungsten bronze (Na_xWO_3) crystals were prepared from a molten mixture of sodium tungstate (Na_2WO_4 ) and tungstic trioxide (WO_3) at 800℃. Crystal structure, lattice parameter, and s
基金This work was supported by the National Natural Science Foundation of China(No.30700747)
文摘Objective:To study the effects of sodium ferulate on the ultrarapid delayed rectifier K+ current(IKur) in human atrial myocytes. Methods:Human atrial myocytes were isolated by enzyme dispersion method. IKur in human atrial myocytes were recorded by using the whole cell patch clamp. The changes of IKur were compared in the absence and the presence of sodium ferulate. Results:There was no effect of 0.4 g/L sodium ferulate on I-V relation of IKur. However, 0.4 g/L sodium ferulate inhibited IKur to some degrees at each test pulse. The current densities of IKur at +60 mV decreased from 4.997 ± 0.35 PA/PF to 3.331 ± 0.26 PA/PF(n = 6, P < 0.05). The inhibitory effect was concentration-dependent. IC50 was(0.41±0.03)g/L and the Hill coefficient was 0.95±0.05. Conclusion:Sodium ferulate as a potassium channel blocker can inhibit IKur in human atrial myocytes effectively.
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(INa) 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.
文摘Neuropathic pain has been hypothesized to be the result of aberrant expression and function of sodium channels at the site of injury. To investigate the effects of NaV1.8 antisense oligonucleotide on the expression of sodium channel mRNA in dorsal root ganglion (DRG) neurons in chronic neuropathic pain. 24 Sprague-Dawley rats weighing 200-260 g were anesthetized with the intraperitoneal injection of 300 mg·kg -1 choral hydrate. The CCI model was made by loose ligation of sciatic nerve trunk by 4-0 chromic gut. The mechanical and thermal pain threshold were measured before operation and 1, 3, 5, 7, 9, 11, 13 days after operation. A PE-10 catheter was implanted in subarachnoid space at lumbar region. On the 7th postoperative day the animals were randomly divided into 4 groups. The drugs were injected intrathecally twice a day for 5 consecutive days in group 2-4. The animals were decapitated 14 days after the surgery. The L4-L6 DRG of the operated side was removed and crushed, and total RNA was extracted with Trizol reagent. The contralateral side was used as control. The change of NaV1.8 sodium channel transcripts was determined by RT-PCR. Pain threshold was significantly lowered after CCI as compared with that in control group and was elevated 3 days after antisense oligonucleotide injection. Sensory neuron specific TTX-R sodium channel NaV1.8 transcript was down-regulated after antisense oligonucleotide injection at the dosage of 45 μg as compared with that in CCI group (P<0.01), and it was even greater at the dosage of 90 μg. The intrathecally injected NaV1.8 antisense oligonucleotide can reduce the mechanical allodynia and thermal hyperalgesia partially by downregulating the SNS transcript expression.