AsKC11, a Kunitz Peptide from Anemonia sulcata,Is a Novel Activator of G Protein-Coupled Inward-Rectifier Potassium Channels     

Dongchen An  Ernesto Lopes Pinheiro-Junior  Lszl Bress  Irina Gladkikh  Elena Leychenko  Eivind A. B. Undheim  Steve Peigneur  Jan Tytgat 《Marine drugs》2022,20(2)

(1) Background: G protein-coupled inward-rectifier potassium (GIRK) channels, especially neuronal GIRK1/2 channels, have been the focus of intense research interest for developing drugs against brain diseases. In this context, venom peptides that selectively activate GIRK channels can be seen as a new source for drug development. Here, we report on the identification and electrophysiological characterization of a novel activator of GIRK1/2 channels, AsKC11, found in the venom of the sea anemone Anemonia sulcata. (2) Methods: AsKC11 was purified from the sea anemone venom by reverse-phase chromatography and the sequence was identified by mass spectrometry. Using the two-electrode voltage-clamp technique, the activity of AsKC11 on GIRK1/2 channels was studied and its selectivity for other potassium channels was investigated. (3) Results: AsKC11, a Kunitz peptide found in the venom of A. sulcata, is the first peptide shown to directly activate neuronal GIRK1/2 channels independent from Gi/o protein activity, without affecting the inward-rectifier potassium channel (IRK1) and with only a minor effect on K_V1.6 channels. Thus, AsKC11 is a novel activator of GIRK channels resulting in larger K⁺ currents because of an increased chord conductance. (4) Conclusions: These discoveries provide new insights into a novel class of GIRK activators.  相似文献   

A Tale of Toxin Promiscuity: The Versatile Pharmacological Effects of Hcr 1b-2 Sea Anemone Peptide on Voltage-Gated Ion Channels     

Ernesto Lopes Pinheiro-Junior  Rimma Kalina  Irina Gladkikh  Elena Leychenko  Jan Tytgat  Steve Peigneur 《Marine drugs》2022,20(2)

Sea anemones are a rich source of biologically active compounds. Among approximately 1100 species described so far, Heteractis crispa species, also known as sebae anemone, is native to the Indo-Pacific area. As part of its venom components, the Hcr 1b-2 peptide was first described as an ASIC1a and ASIC3 inhibitor. Using Xenopus laevis oocytes and the two-electrode voltage-clamp technique, in the present work we describe the remarkable lack of selectivity of this toxin. Besides the acid-sensing ion channels previously described, we identified 26 new targets of this peptide, comprising 14 voltage-gated potassium channels, 9 voltage-gated sodium channels, and 3 voltage-gated calcium channels. Among them, Hcr 1b-2 is the first sea anemone peptide described to interact with isoforms from the Kv7 family and T-type Cav channels. Taken together, the diversity of Hcr 1b-2 targets turns this toxin into an interesting tool to study different types of ion channels, as well as a prototype to develop new and more specific ion channel ligands.  相似文献   

中国沙棘子叶叶肉细胞电流全细胞记录的研究     

朱俊英  闫慧  高荣孚  尹伟伦 《江西农业大学学报》2007,29(5):762-766

实验得出适合膜片钳实验的耐盐木本植物中国沙棘子叶原生质体的游离条件,即取当天脱壳的子叶,放入渗透浓度为0.88 mol/L,pH为5.8,酶液的组分为10 g/LCellulase R-10、0.5 g/LPectolyase Y-23、1.5 g/LMacrozymeR-10、1 g/L Hemicellulase、1 g/L BSA、1 g/L PVP-40、2 mmol/L CaCl2、10 mmol/L Mes和5 mmol/L Vc的溶液中,在26℃、黑暗条件下,静置4 h。并且利用Multiclamp 700B放大器和Clampex 9.2软件,记录到了该原生质体质膜全细胞内向K 通道电流(-459.137 pA及-290.527 pA)和非选择性阳离子通道的外向电流(8.036 pA)。这为沙棘属木本植物细胞的电生理特性及其耐盐性机制关系的研究奠定基础。  相似文献   

Potassium channel gene expression in myocardial sleeves of pulmonary vein and effects of amiodarone on rabbits with rapid atrial pacing     

WANG Jiang-rong  HOU Ying-long  ZHOU Liao-sheng  GAO Mei  SHI Chang-wen  WANG Qing  SUN Ying-ying  LIU Wei 《园艺学报》2007,23(8):1476-1479

  相似文献   

Adipocyte-derived relaxing factor,a new vasodilative factor     

WANG Hao-fan  WANG Hua-dong  QU Yang 《园艺学报》2007,23(8):1649-1653

Although our knowledge of ADRF (adipocyte-derived relaxing factor) is extremely limited,the little that is known has already revealed a promising future in this newly found factor.Firstly,it is secreted by adipose tissue,which is a abundantly and extensively distributed in human body and has become a hot spot for research work in recent years.Secondly,ADRF has shown a significant vasodilative action in a considerable number of experiments conducted on arteries of various sizes,from different body parts of different species of animals,including human.In this article,we introduce the development of ADRF research,sum up its known properties,including its Ca2+,protein tyrosine kinase,and protein kinase A dependent releasing,K+ channel mediated functioning,and interfered effect in different pathological models,and propose problems surrounding this factor and directions for future research work.  相似文献   

飞机草地理分布、危害、传播和防治技术的研究进展   总被引：1，自引：0，他引：1  

莫林  ;张红莲 《广西农学报》2014,(6):44-46

飞机草是一种入侵性杂草,在我国已大面积发生并且仍未得到有效控制。文章对飞机草的地理分布及其对畜牧业、农产品、人畜方面的危害进行阐述,分析其传播途径,并从农业、物理、化学、生物防治技术方面进行探讨并研究其进展,为飞机草的综合防治提供参考资料。  相似文献   

Expression of TMEM16A as a calcium-activated chloride channel in Fischer rat thyroid follicular epithelial cells and its electrophysiologic pro-perties     

HAO Feng  BAI Xue-song  JU Xiao-hong  FANG Fang  ZANG Yu-xuan  ZHU Hang-fei  XIANG Guo-yan  ZHANG Yun-qiao  YUAN Zhong-hai 《园艺学报》2014,30(9):1633-1639

AIM：To investigate the expression of transmembrane protein 16A(TMEM16A) in Fischer rat thyroid follicular epithelial (FRT) cells and its electrophysiologic properties. METHODS：The eukaryotic expression vector of pUB6/V5-TMEM16A was constructed and transfected into FRT cells by liposome-mediated transfection. In order to obtain the high efficiency of gene transfection and expression, the quantity and ratio of lipid/DNA complexes were optimized. The FRT cells stably expressing TMEM16A were gained by the selection with blasticidin and confirmed by the techniques of RT-PCR and immunofluorescence. The expression and location of TMEM16A in the FRT cells were observed under an inverted fluorescence microscope. TMEM16A protein was associated with calcium-dependent chloride current, as measured with halide-sensitive fluorescent protein and patch-clamp technique. RESULTS：The results of double digestion and sequencing indicated that TMEM16A was cloned into pUB6/V5. The results of RT-PCR and immunofluorescence confirmed that TMEM16A was expressed in the FRT cells after transfection with TMEM16A. The classical calcium-activated chloride channel currents were recorded in the FRT cells stably expressing TMEM16A by the technique of patch-clamp and halide-sensitive fluorescent protein YFP-H148Q/I152L. CONCLUSION：The protein expression of TMEM16A in the FRT cells was observed. TMEM16A is the molecular identity of calcium-activated chloride channels.  相似文献   

Effects of Kv1.5 on proliferation and apoptosis of rat PASMCs under hypoxia+hypercapnia condition and relationship with MAPK pathway     

MA Ying-chun  ZHENG Meng-xiao  HUANG Lin-jing  WANG Yuan-yuan  YING Lei  WANG Wan-tie 《园艺学报》2014,30(9):1645-1650

AIM：To investigate the effects of voltage-dependent K＋ channel 1.5 (Kv1.5) on the proliferation and apoptosis of rat pulmonary artery smooth muscle cells (PASMCs) under hypoxia+hypercapnia condition and the relationship with mitogen-activated protein kinase(MAPK) signal pathway. METHODS：The PASMCs isolated from the male SD rat were cultured under hypoxia+hypercapnia condition, and randomly divided into normal group (N group), hypoxia+hypercapnia group (HH group), hypoxia+hypercapnia+DMSO incubation group (HD group), hypoxia+hypercapnia+U0126 (an extracellular signal-regulated kinase 1/2 inhibitor) incubation group (HU group), hypoxia+hypercapnia+SB203580 (a p38 mitogen-activated protein kinase inhibitor) incubation group (HS group), and hypoxia+hypercapnia+anisomycin (an agonist of MAPK) incubation group (HA group). Cell Counting Kit-8 was used to detect the cell viability. The protein expression of Kv1.5, PCNA and Bax was detected by Western blotting. RESULTS：Compared with N group, the cell viability and PCNA protein expression in HH group and HD group were significantly raised (P<001), but Kv1.5 and Bax proteins were significantly decreased (P<0.01). No difference between HH group and HD group was observed (P>005). Compared with HD group, the cell viability and PCNA protein expression in HU group, HS group and HA group were decreased (P<0.05 or P<0.01), but Kv1.5 protein and Bax protein were raised (P<0.01), with the most significant changes in HA group. ^{CONCLUSION：}The regulation of Kv1.5 to the proliferation and apoptosis of PASMCs under hypoxia+hypercapnia condition might have a relationship with the activation of MAPK signal pathway.  相似文献   

Action of Clathrodin and Analogues on Voltage-Gated Sodium Channels     

Steve Peigneur  Ale? ?ula  Nace Zidar  Fiona Chan-Porter  Robert Kirby  David Madge  Janez Ila?  Danijel Kikelj  Jan Tytgat 《Marine drugs》2014,12(4):2132-2143

Clathrodin is a marine alkaloid and believed to be a modulator of voltage-gated sodium (Na_V ) channels. Since there is an urgent need for small molecule Na_V channel ligands as novel therapeutics, clathrodin could represent an interesting lead compound. Therefore, clathrodin was reinvestigated for its potency and Na_V channel subtype selectivity. Clathrodin and its synthetic analogues were subjected to screening on a broad range of Na_V channel isoforms, both in voltage clamp and patch clamp conditions. Even though clathrodin was not found to exert any activity, some analogues were capable of modulating the Na_V channels, hereby validating the pyrrole-2-aminoimidazole alkaloid structure as a core structure for future small molecule-based Na_V channel modulators.  相似文献   

彩票投注视频监控管理系统的设计与实现     

高军  李合君 《湖南农业大学学报(自然科学版)》2014,(3):120-122

清代是书院儒学传播的最重要时期之一,清代书院对士人日常教育的主要内容是儒学。日常讲学承担了书院的主体教育职能,无疑成为书院最主要的儒学传播途径。其特点是“半教半学”,非常重视师友砥砺、形成亲密的师生关系,使生徒潜移默化地受到影响;藏书、刻书是书院的重要特征,也是儒学传播的重要途径;祭祀作为书院规制的重要组成部分,是确立儒家道统的重要载体和途径,从精神信仰层面传播儒学。此外,书院还通过命名题额、嵌碑立石、匾联语录等多种环境熏陶途径将生徒纳入到儒学的精神世界中。  相似文献