The effects of rises in external K+(Kext) were examined on the hyperpolarization-activated cation current(Ih) in rat dorsal root ganglion neurons using the whole-cell patch clamp technique.The results showed that Kext...The effects of rises in external K+(Kext) were examined on the hyperpolarization-activated cation current(Ih) in rat dorsal root ganglion neurons using the whole-cell patch clamp technique.The results showed that Kext increased Ih in a certain concentration and voltage-dependent manner.At the basal Kext level(4 mmol/L),Ih had a maximal amplitude of 1085 ± 340 pA which was enhanced by ～45% and ～92% at 8 and 16 mmol/L Kext,respectively.The midpoint activation voltage was significantly shifted from -98 mV in the hyperpolarizing direction by 8 and 12 mV at 8 and 16 mmol/L Kext,respectively with alteration of the activation course of Ih.The short time constants of activation became longer with the increasing amplitude of the command potential upon rises in Kext.The long time constants became shorter.The reversal potentials were shifted in the positive direction without significant alterations upon rises in Kext.According to the functional role of Ih,Kext increased Ih,resulting in an enhanced neuronal excitability,which might produce activation potential abnormality and perhaps neuropathic pain involved.展开更多
AIM： To assess the role of hyperpolarization-activated cyclic nucleotide-gated cation （HCN） channels in regu- lating the excitability of vagal and spinal gut afferents. METHODS： The mechanosensory response of mese...AIM： To assess the role of hyperpolarization-activated cyclic nucleotide-gated cation （HCN） channels in regu- lating the excitability of vagal and spinal gut afferents. METHODS： The mechanosensory response of mesen- teric afferent activity was measured in an ex vivo murine jejunum preparation. HCN channel activity was recorded through voltage and current clamp in acutely dissoci- ated dorsal root ganglia （DRG） and nodose ganglia （NG） neurons retrogradely labeled from the small intestine through injection of a fluorescent marker （DiI）. The isoforms of HCN channels expressed in DRG and NG neurons were examined by immunohistochemistry. RESULTS： Ramp distension of the small intestine evok- ed biphasic increases in the afferent nerve activity, re- flecting the activation of low- and high-threshold fibers.HCN blocker CsCl （5 mmol/L） preferentially inhibited the responses of low-threshold fibers to distension and showed no significant effects on the high-threshold re- sponses. The effect of CsCI was mimicked by the more selective HCN blocker ZD7288 （10 ~mol/L）. In 71.4% of DiI labeled DRG neurons （/7 = 20） and 90.9% of DiI labeled NG neurons （n = 10）, an inward current （Ih current） was evoked by hyperpolarization pulses which was fully eliminated by extracellular CsCI. In neurons expressing Ih current, a typical ＂sag＂ was observed upon injection of hyperpolarizing current pulses in cur- rent-clamp recordings. CsCI abolished the sag entirely. In some DiI labeled DRG neurons, the Ih current was potentiated by 8-Br-cAMP, which had no effect on the Ih current of DiI labeled NG neurons. Immunohistochem- istry revealed differential expression of HCN isoforms in vagal and spinal afferents, and HCN2 and HCN3 seemed to be the dominant isoform in DRG and NG, respec- tively.CONCLUSION： HCNs differentially regulate the excit- ability of vagal and spinal afferent of murine small in- testine.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
Objectives Recent studies have described regional differences in the electrophysiology and pharmacology of ventric- ular myocardium in canine, feline, rat, guinea pig, and human hearts. This has been shown to be due t...Objectives Recent studies have described regional differences in the electrophysiology and pharmacology of ventric- ular myocardium in canine, feline, rat, guinea pig, and human hearts. This has been shown to be due to a smaller IKs and a lager sodium-calcium exchange current （INa-Ca） and late INa in M region （ deep subepicardial to midmyocardial）. Studies from our laboratory have found a new repolarization current-nonselective cation current （NSCCs） existing in rabbit fight ventricular myocytes. Methods We examined the characteristics of NSCCs in epicardial, M region, and endocardial cells isolated from the rabbit left ventricle with standard microelectrode and whole-cell patch-clamp tech- niques. The permeability to Na^＋ , K^＋ , Li^＋ , Cs^＋ but not to Cl^- indicating that it was a nonselective cation current. Gd^＋3 （0. 1 mmol/1） and La^3＋ （0. 1 retool/1 ） can block the current markedly. Results Further characterization of NSCCs was significantly smaller in M cells than in epicardial and endocardial cells. NSCCs current density was significantly smaller in M cells than in epicardial and endocardial cells. With repolarization to - 80 mV, INa current density was （ -0. 44 ±0. 05） PA/PF in endocardial cells, （ -0. 12 ±0. 05） PA/PF in M cells and （ - 0. 28 ±0. 07） PA/PF in epicardial cells ; and with repolarization to ＋ 30 mV, INa, current density was （ 1.09 ± 0. 29） PA/PF in endocardial cells, （0. 38±0. 09） PA/PF in M cells and （0. 91 ± 0. 32） PA/PF in epicardial cells. Conclusions Transmural dispersion of repolarization was due to the heterogeneity of NSCCs in rabbit left ventricle epicardial, endocardial myocytes and M cells. These findings may advance our understanding of the ionic basis for our understanding of factors contributing to the development of cardiac arrhythmias.展开更多
This contribution is not only intended to provide a fresh review for researches on static electrification, but also contains a sub- stantial amount of new material with a view of closing some gaps in the present state...This contribution is not only intended to provide a fresh review for researches on static electrification, but also contains a sub- stantial amount of new material with a view of closing some gaps in the present state of knowledge of oil streaming electrification. In this paper, the Electrostatic Charging Tendency (ECT) of fresh (unaged) and aged transformer oils were investigated in a spinning disk system. Static electrification measurement at different aging degrees was carried out under laboratory controlled conditions. Changes in static elec- trification were compared to some classical aging indexes (conductivity, dissipation factor, water content, resistivity, etc.). Fast, inexpensive and reliable laboratory testing procedures developed by American Society for Testing Materials (D 6802 and D 6181) were also used to monitor decay products as trace impurities. The obtained results show that static electrification currents increase with temperature, fluid mo- tion velocity, surface properties and the aging byproducts of the oil. The polarity, the amplitude and the time constant of the electrification currents are also affected. The results show that static electrification has relationship with thermal aging and is sensitive to turbidimetric and spectrophotometric measurements.展开更多
The prelimbic cortex(PL)plays a critical role in processing both the sensory and affective components of pain.However,the underlying molecular mechanisms remain poorly understood.In this study,we observed a reduction ...The prelimbic cortex(PL)plays a critical role in processing both the sensory and affective components of pain.However,the underlying molecular mechanisms remain poorly understood.In this study,we observed a reduction in hyperpolarization-activated cation current(Ih)in layer V pyramidal neurons of the contralateral PL in a mouse model of spared nerve injury(SNI).The expression of hyperpolarization-activated cyclic nucleotide-gated 2(HCN2)channels was also decreased in the contralateral PL.Conversely,microinjection of fisetin,a partial agonist of HCN2,produced both analgesic and anxiolytic effects.Additionally,we found that cyclin-dependent kinase 5(CDK5)was activated in the contralateral PL,where it formed a complex with HCN2 and phosphorylated its C-terminus.Knockdown of CDK5 restored HCN2 expression and alleviated both pain hypersensitivity and anxiety-like behaviors.Collectively,these results indicate that CDK5-mediated dysfunction of HCN2 in the PL underlies nerve injury-induced mechanical hypersensitivity and anxiety.展开更多
基金Supported by the University of Science and Technology Foundation of Shanxi Province (Grant No. 200713010)
文摘The effects of rises in external K+(Kext) were examined on the hyperpolarization-activated cation current(Ih) in rat dorsal root ganglion neurons using the whole-cell patch clamp technique.The results showed that Kext increased Ih in a certain concentration and voltage-dependent manner.At the basal Kext level(4 mmol/L),Ih had a maximal amplitude of 1085 ± 340 pA which was enhanced by ～45% and ～92% at 8 and 16 mmol/L Kext,respectively.The midpoint activation voltage was significantly shifted from -98 mV in the hyperpolarizing direction by 8 and 12 mV at 8 and 16 mmol/L Kext,respectively with alteration of the activation course of Ih.The short time constants of activation became longer with the increasing amplitude of the command potential upon rises in Kext.The long time constants became shorter.The reversal potentials were shifted in the positive direction without significant alterations upon rises in Kext.According to the functional role of Ih,Kext increased Ih,resulting in an enhanced neuronal excitability,which might produce activation potential abnormality and perhaps neuropathic pain involved.
基金Supported by Science and Technology Commission of Shanghai Municipality,No. 10ZR1417300Educational Commission of Shanghai Municipality,No. 10ZZ69
文摘AIM： To assess the role of hyperpolarization-activated cyclic nucleotide-gated cation （HCN） channels in regu- lating the excitability of vagal and spinal gut afferents. METHODS： The mechanosensory response of mesen- teric afferent activity was measured in an ex vivo murine jejunum preparation. HCN channel activity was recorded through voltage and current clamp in acutely dissoci- ated dorsal root ganglia （DRG） and nodose ganglia （NG） neurons retrogradely labeled from the small intestine through injection of a fluorescent marker （DiI）. The isoforms of HCN channels expressed in DRG and NG neurons were examined by immunohistochemistry. RESULTS： Ramp distension of the small intestine evok- ed biphasic increases in the afferent nerve activity, re- flecting the activation of low- and high-threshold fibers.HCN blocker CsCl （5 mmol/L） preferentially inhibited the responses of low-threshold fibers to distension and showed no significant effects on the high-threshold re- sponses. The effect of CsCI was mimicked by the more selective HCN blocker ZD7288 （10 ~mol/L）. In 71.4% of DiI labeled DRG neurons （/7 = 20） and 90.9% of DiI labeled NG neurons （n = 10）, an inward current （Ih current） was evoked by hyperpolarization pulses which was fully eliminated by extracellular CsCI. In neurons expressing Ih current, a typical ＂sag＂ was observed upon injection of hyperpolarizing current pulses in cur- rent-clamp recordings. CsCI abolished the sag entirely. In some DiI labeled DRG neurons, the Ih current was potentiated by 8-Br-cAMP, which had no effect on the Ih current of DiI labeled NG neurons. Immunohistochem- istry revealed differential expression of HCN isoforms in vagal and spinal afferents, and HCN2 and HCN3 seemed to be the dominant isoform in DRG and NG, respec- tively.CONCLUSION： HCNs differentially regulate the excit- ability of vagal and spinal afferent of murine small in- testine.
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Objectives Recent studies have described regional differences in the electrophysiology and pharmacology of ventric- ular myocardium in canine, feline, rat, guinea pig, and human hearts. This has been shown to be due to a smaller IKs and a lager sodium-calcium exchange current （INa-Ca） and late INa in M region （ deep subepicardial to midmyocardial）. Studies from our laboratory have found a new repolarization current-nonselective cation current （NSCCs） existing in rabbit fight ventricular myocytes. Methods We examined the characteristics of NSCCs in epicardial, M region, and endocardial cells isolated from the rabbit left ventricle with standard microelectrode and whole-cell patch-clamp tech- niques. The permeability to Na^＋ , K^＋ , Li^＋ , Cs^＋ but not to Cl^- indicating that it was a nonselective cation current. Gd^＋3 （0. 1 mmol/1） and La^3＋ （0. 1 retool/1 ） can block the current markedly. Results Further characterization of NSCCs was significantly smaller in M cells than in epicardial and endocardial cells. NSCCs current density was significantly smaller in M cells than in epicardial and endocardial cells. With repolarization to - 80 mV, INa current density was （ -0. 44 ±0. 05） PA/PF in endocardial cells, （ -0. 12 ±0. 05） PA/PF in M cells and （ - 0. 28 ±0. 07） PA/PF in epicardial cells ; and with repolarization to ＋ 30 mV, INa, current density was （ 1.09 ± 0. 29） PA/PF in endocardial cells, （0. 38±0. 09） PA/PF in M cells and （0. 91 ± 0. 32） PA/PF in epicardial cells. Conclusions Transmural dispersion of repolarization was due to the heterogeneity of NSCCs in rabbit left ventricle epicardial, endocardial myocytes and M cells. These findings may advance our understanding of the ionic basis for our understanding of factors contributing to the development of cardiac arrhythmias.
文摘This contribution is not only intended to provide a fresh review for researches on static electrification, but also contains a sub- stantial amount of new material with a view of closing some gaps in the present state of knowledge of oil streaming electrification. In this paper, the Electrostatic Charging Tendency (ECT) of fresh (unaged) and aged transformer oils were investigated in a spinning disk system. Static electrification measurement at different aging degrees was carried out under laboratory controlled conditions. Changes in static elec- trification were compared to some classical aging indexes (conductivity, dissipation factor, water content, resistivity, etc.). Fast, inexpensive and reliable laboratory testing procedures developed by American Society for Testing Materials (D 6802 and D 6181) were also used to monitor decay products as trace impurities. The obtained results show that static electrification currents increase with temperature, fluid mo- tion velocity, surface properties and the aging byproducts of the oil. The polarity, the amplitude and the time constant of the electrification currents are also affected. The results show that static electrification has relationship with thermal aging and is sensitive to turbidimetric and spectrophotometric measurements.
基金supported by the National Natural Science Foundation of China(32030052,W2411014 to Yun Wang,32271190 and 31972905 to Ying Zhang)the STI 2030 Major Project of the Ministry of Science and Technology of China(2021ZD0203204)the Beijing Natural Science Foundation(QY23067).
文摘The prelimbic cortex(PL)plays a critical role in processing both the sensory and affective components of pain.However,the underlying molecular mechanisms remain poorly understood.In this study,we observed a reduction in hyperpolarization-activated cation current(Ih)in layer V pyramidal neurons of the contralateral PL in a mouse model of spared nerve injury(SNI).The expression of hyperpolarization-activated cyclic nucleotide-gated 2(HCN2)channels was also decreased in the contralateral PL.Conversely,microinjection of fisetin,a partial agonist of HCN2,produced both analgesic and anxiolytic effects.Additionally,we found that cyclin-dependent kinase 5(CDK5)was activated in the contralateral PL,where it formed a complex with HCN2 and phosphorylated its C-terminus.Knockdown of CDK5 restored HCN2 expression and alleviated both pain hypersensitivity and anxiety-like behaviors.Collectively,these results indicate that CDK5-mediated dysfunction of HCN2 in the PL underlies nerve injury-induced mechanical hypersensitivity and anxiety.
