Slow inward currents are known as neuronal excitatory currents mediated by glutamate release and activation of neuronal extra synaptic N-met hyl-D-aspartate receptors with the contribution of astrocytes.These events a...Slow inward currents are known as neuronal excitatory currents mediated by glutamate release and activation of neuronal extra synaptic N-met hyl-D-aspartate receptors with the contribution of astrocytes.These events are significantly slower than the excitatory postsynaptic currents.Parameters of slow inward currents are determined by seve ral factors including the mechanisms of astrocytic activation and glutamate release,as well as the diffusion pathways from the release site towards the extra synaptic recepto rs.Astrocytes are stimulated by neuronal network activity,which in turn excite neurons,forming an astrocyte-neuron feedback loop.Mostly as a consequence of brain edema,astrocytic swelling can also induce slow inward currents under pathological conditions.There is a growing body of evidence on the roles of slow inward currents on a single neuron or local network level.These events often occur in synchro ny on neurons located in the same astrocytic domain.Besides synchronization of neuronal excitability,slow inward currents also set synaptic strength via eliciting timing-dependent synaptic plasticity.In addition,slow inward currents are also subject to non-synaptic plasticity triggered by long-la sting stimulation of the excitatory inputs.Of note,there might be important regionspecific differences in the roles and actions triggering slow inward currents.In greater networks,the pathophysiological roles of slow inward currents can be better understood than physiological ones.Slow inward currents are identified in the pathophysiological background of autism,as slow inward currents drive early hypersynchrony of the neural networks.Slow inward currents are significant contributors to paroxysmal depolarizational shifts/interictal spikes.These events are related to epilepsy,but also found in Alzheimer's disease,Parkinson's disease,and stroke,leading to the decline of cognitive functions.Events with features overlapping with slow inward currents(excitatory,N-methyl-Daspartate-receptor mediated currents with astrocytic contribution) as ischemic currents and spreading depolarization also have a well-known pathophysiological role in worsening consequences of stroke,traumatic brain injury,or epilepsy.One might assume that slow inward currents occurring with low frequency under physiological conditions might contribute to synaptic plasticity and memory formation.However,to state this,more experimental evidence from greater neuronal networks or the level of the individual is needed.In this review,I aimed to summarize findings on slow inward currents and to speculate on the potential functions of it.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
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
莲心碱(Lien)10～100μmol/L可浓度依赖性地降低离体兔窦房结(SAN)起搏细胞慢反应动作电位幅度(APA)及零相最大上升速率((?)_(max)),延长窦性周长(SCL),并可明显拮抗Bay K 8644增大SAN起搏细胞及高K^-诱发的豚鼠乳头肌慢反应动作电位的...莲心碱(Lien)10～100μmol/L可浓度依赖性地降低离体兔窦房结(SAN)起搏细胞慢反应动作电位幅度(APA)及零相最大上升速率((?)_(max)),延长窦性周长(SCL),并可明显拮抗Bay K 8644增大SAN起搏细胞及高K^-诱发的豚鼠乳头肌慢反应动作电位的APA和((?)_(max))作用。Lien 1～100 μmol/L还可浓度依赖性地抑制犬浦氏纤维慢内向电流(I_(si)),3和100μmol/L分别使I_(si)峰值下降14和88%。结果表明Lien具有抗钙作用。展开更多
目的观察比索洛尔对容量超负荷心衰大鼠左室心肌细胞内向整流钾电流((I_(K1))的影响。方法成年雄性SD大鼠(180-200 g)随机分为假手术组、心衰组和比索洛尔干预组,采用腹主动脉-下腔静脉穿刺造瘘法制作容量超负荷心衰模型。术后8周,比索...目的观察比索洛尔对容量超负荷心衰大鼠左室心肌细胞内向整流钾电流((I_(K1))的影响。方法成年雄性SD大鼠(180-200 g)随机分为假手术组、心衰组和比索洛尔干预组,采用腹主动脉-下腔静脉穿刺造瘘法制作容量超负荷心衰模型。术后8周,比索洛尔干预组给予比索洛尔(1 mg/kg,1次/d)灌胃,干预4周后,检测血清脑钠肽(BNP)及超声心动图以评价心功能。急性酶解法分离大鼠左室心肌细胞,采用全细胞膜片钳技术记录动作电位及I_(K1)电流,并绘制I-V曲线。结果心衰组与假手术组大鼠比较,心功能明显下降,血清BNP水平(pmol/L)明显升高(1 562.89±153.26 vs 225.57±63.62,P<0.01),动作电位时程(APD,ms)延长(APD_(90):324.85±21.66 vs 137.80±15.24,P<0.01),I_(K1)电流密度减小(-140 m V:-23.20±2.10 vs-35.55±2.78,P<0.01)。比索洛尔干预可明显改善心功能,缩短APD,增加I_(K1)电流密度(-140 m V:-27.16±2.62vs-23.20±2.10,P<0.01)。结论比索洛尔干预可改善慢性心衰大鼠的心功能,增加I_(K1)电流密度。展开更多
基金funded by the National Research Developm ent and Innovation Office (NKFIH-K1468 73) (to BP)。
文摘Slow inward currents are known as neuronal excitatory currents mediated by glutamate release and activation of neuronal extra synaptic N-met hyl-D-aspartate receptors with the contribution of astrocytes.These events are significantly slower than the excitatory postsynaptic currents.Parameters of slow inward currents are determined by seve ral factors including the mechanisms of astrocytic activation and glutamate release,as well as the diffusion pathways from the release site towards the extra synaptic recepto rs.Astrocytes are stimulated by neuronal network activity,which in turn excite neurons,forming an astrocyte-neuron feedback loop.Mostly as a consequence of brain edema,astrocytic swelling can also induce slow inward currents under pathological conditions.There is a growing body of evidence on the roles of slow inward currents on a single neuron or local network level.These events often occur in synchro ny on neurons located in the same astrocytic domain.Besides synchronization of neuronal excitability,slow inward currents also set synaptic strength via eliciting timing-dependent synaptic plasticity.In addition,slow inward currents are also subject to non-synaptic plasticity triggered by long-la sting stimulation of the excitatory inputs.Of note,there might be important regionspecific differences in the roles and actions triggering slow inward currents.In greater networks,the pathophysiological roles of slow inward currents can be better understood than physiological ones.Slow inward currents are identified in the pathophysiological background of autism,as slow inward currents drive early hypersynchrony of the neural networks.Slow inward currents are significant contributors to paroxysmal depolarizational shifts/interictal spikes.These events are related to epilepsy,but also found in Alzheimer's disease,Parkinson's disease,and stroke,leading to the decline of cognitive functions.Events with features overlapping with slow inward currents(excitatory,N-methyl-Daspartate-receptor mediated currents with astrocytic contribution) as ischemic currents and spreading depolarization also have a well-known pathophysiological role in worsening consequences of stroke,traumatic brain injury,or epilepsy.One might assume that slow inward currents occurring with low frequency under physiological conditions might contribute to synaptic plasticity and memory formation.However,to state this,more experimental evidence from greater neuronal networks or the level of the individual is needed.In this review,I aimed to summarize findings on slow inward currents and to speculate on the potential functions of it.
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.
文摘莲心碱(Lien)10～100μmol/L可浓度依赖性地降低离体兔窦房结(SAN)起搏细胞慢反应动作电位幅度(APA)及零相最大上升速率((?)_(max)),延长窦性周长(SCL),并可明显拮抗Bay K 8644增大SAN起搏细胞及高K^-诱发的豚鼠乳头肌慢反应动作电位的APA和((?)_(max))作用。Lien 1～100 μmol/L还可浓度依赖性地抑制犬浦氏纤维慢内向电流(I_(si)),3和100μmol/L分别使I_(si)峰值下降14和88%。结果表明Lien具有抗钙作用。
文摘目的观察比索洛尔对容量超负荷心衰大鼠左室心肌细胞内向整流钾电流((I_(K1))的影响。方法成年雄性SD大鼠(180-200 g)随机分为假手术组、心衰组和比索洛尔干预组,采用腹主动脉-下腔静脉穿刺造瘘法制作容量超负荷心衰模型。术后8周,比索洛尔干预组给予比索洛尔(1 mg/kg,1次/d)灌胃,干预4周后,检测血清脑钠肽(BNP)及超声心动图以评价心功能。急性酶解法分离大鼠左室心肌细胞,采用全细胞膜片钳技术记录动作电位及I_(K1)电流,并绘制I-V曲线。结果心衰组与假手术组大鼠比较,心功能明显下降,血清BNP水平(pmol/L)明显升高(1 562.89±153.26 vs 225.57±63.62,P<0.01),动作电位时程(APD,ms)延长(APD_(90):324.85±21.66 vs 137.80±15.24,P<0.01),I_(K1)电流密度减小(-140 m V:-23.20±2.10 vs-35.55±2.78,P<0.01)。比索洛尔干预可明显改善心功能,缩短APD,增加I_(K1)电流密度(-140 m V:-27.16±2.62vs-23.20±2.10,P<0.01)。结论比索洛尔干预可改善慢性心衰大鼠的心功能,增加I_(K1)电流密度。
