目的:探讨缬沙坦对自发高血压大鼠(SHR)左室肥厚心肌Kv4.2表达的影响。方法:将16只10周龄雄性SHR随机分成缬沙坦组和非缬沙坦组各8只:8只10周龄Wistar-Kyoto大鼠为对照组。喂药8周后分别测定各组大鼠动脉收缩压、左室质量指数(LVMI)、...目的:探讨缬沙坦对自发高血压大鼠(SHR)左室肥厚心肌Kv4.2表达的影响。方法:将16只10周龄雄性SHR随机分成缬沙坦组和非缬沙坦组各8只:8只10周龄Wistar-Kyoto大鼠为对照组。喂药8周后分别测定各组大鼠动脉收缩压、左室质量指数(LVMI)、左室心肌Kv4.2的表达。结果:非缬沙坦组和缬沙坦组LVMI明显大于对照组(3.7+0.02 mg/g and 3.2-0.03mg/g vs 2.5±0.03mg/g,P<0.0叭),非缬沙坦组LVMI明显大于缬沙坦组(3.7±+0.02 mg/g vs 3.2+0.03 mg/g,P<0.001);非缬沙坦组和缬沙坦组左心室心肌Kv4.2表达明显低于对照组(P<0.01),缬沙坦组左心室心肌Kv4.2的表达明显高于非缬沙坦组(P<0.01)。结论:缬沙坦通过逆转SHR左室心肌肥厚提高左室心肌Kv4.2的表达。展开更多
Genome-wide studies have reported that Parkinson's disease is associated with abnormal expression of various growth factors. In this study, male C57BL/6 mice aged 10 weeks were used to establish Parkinson's di...Genome-wide studies have reported that Parkinson's disease is associated with abnormal expression of various growth factors. In this study, male C57BL/6 mice aged 10 weeks were used to establish Parkinson's disease models using an intraperitoneal injection of 60 mg/kg 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine. 28 days later, 10 or 100 ng fibroblast growth factor 20 was injected intracerebroventricularly. The electrophysiological changes in the mouse hippocampus were recorded using a full-cell patch clamp. Expression of Kv4.2 in the substantia nigra was analyzed using a western blot assay. Serum malondialdehyde levels were analyzed by enzyme-linked immunosorbent assay. The motor coordination of mice was evaluated using the rotarod test. The results showed that fibroblast growth factor 20 decreased A-type potassium current in neurons of the substantia nigra, increased long-term potentiation amplitude in the hippocampus, and downregulated Kv4.2 expression. A high dose of fibroblast growth factor 20 reduced serum malondialdehyde levels and enhanced the motor coordination of mice. These findings confirm that fibroblast growth factor 20 has a therapeutic effect on the toxicity induced by l-methyl-4-phenyl-l,2,3s6-tetrahydropyridine, and its mechanism of action is associated with the inhibition of A-type K^+ currents and Kv4.2 expression. All animal procedures were approved by the Animal Care and Use Committee of Qilu Hospital of Shandong University, China in 2017 (approval No. KYLL-2017-0012).展开更多
目的观察甲基苯丙胺(Meth)对瞬时外向钾电流的影响及原因。方法将怀孕18 d SD大鼠胎鼠海马神经元分为对照组和Meth处理组,利用全细胞膜片钳方法记录外向瞬时钾电流变化;采用原位末端转移酶标记技术(TUNEL)观察Meth引起的细胞损伤作用;...目的观察甲基苯丙胺(Meth)对瞬时外向钾电流的影响及原因。方法将怀孕18 d SD大鼠胎鼠海马神经元分为对照组和Meth处理组,利用全细胞膜片钳方法记录外向瞬时钾电流变化;采用原位末端转移酶标记技术(TUNEL)观察Meth引起的细胞损伤作用;利用逆转录聚合酶链反应(RT-PCR)方法观察瞬时外向电流成分中Kv1.4、4.1、4.2和4.3表达,并通过western-blot方法观察Kv4.2蛋白表达。结果与对照组[(87.4±12.5)pA/pF]比较,Meth能引起瞬时外向钾电流增大[(120.1±19.6)pA/pF](P<0.01),与对照组(1.00±0.18)比较,Meth处理组凋亡率为对照组的(7.11±0.95)倍(P<0.01),钾通道抑制剂4-氨基吡啶(4-AP)明显抑制神经元凋亡(P<0.01);Kv4.2可能是外向电流成分中主要贡献者,Meth能上调Kv4.2通道蛋白表达;与Kv4.2上调密切相关的Kchip2/3、Kchip4、CaMK2蛋白表达增高。结论 Meth引起的瞬时钾电流增大可能通过Kv4.2上调来实现,但其机制仍需进一步探讨。展开更多
In the mammalian brain, information encoding and storage have been explained by revealing the cellular and molecular mechanisms of synaptic plasticity at various levels in the central nervous system, including the hip...In the mammalian brain, information encoding and storage have been explained by revealing the cellular and molecular mechanisms of synaptic plasticity at various levels in the central nervous system, including the hippocampus and the cerebral cortices. The modulatory mechanisms of synaptic excitability that are correlated with neuronal tasks are fundamental factors for synaptic plasticity, and they are dependent on intracellular Ca2＋-mediated signaling. In the present review, the A-type K＋ （IA） channel, one of the voltage-dependent cation channels, is considered as a key player in the modulation of Ca2＋ influx through synaptic NMDA receptors and their correlated signaling pathways. The cellular functions of IA channels indicate that they possibly play as integral parts of synaptic and somatic complexes, completing the initiation and stabilization of memory.展开更多
基金This work was supported by the National Basic Research Priorities Programme of China (No. 1998051106) National High TECH Research and Development Programme of China ( No. 2001AA234021).
文摘目的:探讨缬沙坦对自发高血压大鼠(SHR)左室肥厚心肌Kv4.2表达的影响。方法:将16只10周龄雄性SHR随机分成缬沙坦组和非缬沙坦组各8只:8只10周龄Wistar-Kyoto大鼠为对照组。喂药8周后分别测定各组大鼠动脉收缩压、左室质量指数(LVMI)、左室心肌Kv4.2的表达。结果:非缬沙坦组和缬沙坦组LVMI明显大于对照组(3.7+0.02 mg/g and 3.2-0.03mg/g vs 2.5±0.03mg/g,P<0.0叭),非缬沙坦组LVMI明显大于缬沙坦组(3.7±+0.02 mg/g vs 3.2+0.03 mg/g,P<0.001);非缬沙坦组和缬沙坦组左心室心肌Kv4.2表达明显低于对照组(P<0.01),缬沙坦组左心室心肌Kv4.2的表达明显高于非缬沙坦组(P<0.01)。结论:缬沙坦通过逆转SHR左室心肌肥厚提高左室心肌Kv4.2的表达。
文摘Genome-wide studies have reported that Parkinson's disease is associated with abnormal expression of various growth factors. In this study, male C57BL/6 mice aged 10 weeks were used to establish Parkinson's disease models using an intraperitoneal injection of 60 mg/kg 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine. 28 days later, 10 or 100 ng fibroblast growth factor 20 was injected intracerebroventricularly. The electrophysiological changes in the mouse hippocampus were recorded using a full-cell patch clamp. Expression of Kv4.2 in the substantia nigra was analyzed using a western blot assay. Serum malondialdehyde levels were analyzed by enzyme-linked immunosorbent assay. The motor coordination of mice was evaluated using the rotarod test. The results showed that fibroblast growth factor 20 decreased A-type potassium current in neurons of the substantia nigra, increased long-term potentiation amplitude in the hippocampus, and downregulated Kv4.2 expression. A high dose of fibroblast growth factor 20 reduced serum malondialdehyde levels and enhanced the motor coordination of mice. These findings confirm that fibroblast growth factor 20 has a therapeutic effect on the toxicity induced by l-methyl-4-phenyl-l,2,3s6-tetrahydropyridine, and its mechanism of action is associated with the inhibition of A-type K^+ currents and Kv4.2 expression. All animal procedures were approved by the Animal Care and Use Committee of Qilu Hospital of Shandong University, China in 2017 (approval No. KYLL-2017-0012).
文摘目的观察甲基苯丙胺(Meth)对瞬时外向钾电流的影响及原因。方法将怀孕18 d SD大鼠胎鼠海马神经元分为对照组和Meth处理组,利用全细胞膜片钳方法记录外向瞬时钾电流变化;采用原位末端转移酶标记技术(TUNEL)观察Meth引起的细胞损伤作用;利用逆转录聚合酶链反应(RT-PCR)方法观察瞬时外向电流成分中Kv1.4、4.1、4.2和4.3表达,并通过western-blot方法观察Kv4.2蛋白表达。结果与对照组[(87.4±12.5)pA/pF]比较,Meth能引起瞬时外向钾电流增大[(120.1±19.6)pA/pF](P<0.01),与对照组(1.00±0.18)比较,Meth处理组凋亡率为对照组的(7.11±0.95)倍(P<0.01),钾通道抑制剂4-氨基吡啶(4-AP)明显抑制神经元凋亡(P<0.01);Kv4.2可能是外向电流成分中主要贡献者,Meth能上调Kv4.2通道蛋白表达;与Kv4.2上调密切相关的Kchip2/3、Kchip4、CaMK2蛋白表达增高。结论 Meth引起的瞬时钾电流增大可能通过Kv4.2上调来实现,但其机制仍需进一步探讨。
基金supported by the 2014 Scientific Promotion Program funded by Jeju National University, Korea
文摘In the mammalian brain, information encoding and storage have been explained by revealing the cellular and molecular mechanisms of synaptic plasticity at various levels in the central nervous system, including the hippocampus and the cerebral cortices. The modulatory mechanisms of synaptic excitability that are correlated with neuronal tasks are fundamental factors for synaptic plasticity, and they are dependent on intracellular Ca2＋-mediated signaling. In the present review, the A-type K＋ （IA） channel, one of the voltage-dependent cation channels, is considered as a key player in the modulation of Ca2＋ influx through synaptic NMDA receptors and their correlated signaling pathways. The cellular functions of IA channels indicate that they possibly play as integral parts of synaptic and somatic complexes, completing the initiation and stabilization of memory.
