Background： The intestinal epithelium is an important barrier that depends on a complex mixture of proteins and these proteins comprise different intercellular junctions. The purpose of this study was to investigate ...Background： The intestinal epithelium is an important barrier that depends on a complex mixture of proteins and these proteins comprise different intercellular junctions. The purpose of this study was to investigate the postnatal and developmental changes in morphology, intercellular junctions and voltage-gated potassium（Kv） channels in the intestine of piglets during the suckling and post-weaning periods.Results： Samples of the small intestine were obtained from 1-, 7-, 14-, and 21-d-old suckling piglets and piglets on d 1, 3, 5, and 7 after weaning at 14 d of age. The results showed that the percentage of proliferating cell nuclear antigen（PCNA）-positive cells and alkaline phosphatase（AKP） activity, as well as the abundances of E-cadherin,occludin, and Kv1.5 m RNA and claudin-1, claudin-3, and occludin protein in the jejunum were increased from d 1to d 21 during the suckling period（P 〈 0.05）. Weaning induced decreases in the percentage of PCNA-positive cells,AKP activity and the abundances of E-cadherin, occludin and zonula occludens（ZO）-1 m RNA or protein in the jejunum on d 1, 3 and 5 post-weaning（P 〈 0.05）. There were lower abundances of E-cadherin, occludin and ZO-1m RNA as well as claudin-1, claudin-3 and ZO-1 protein in the jejunum of weanling piglets than in 21-d-old suckling piglets（P 〈 0.05）. The abundances of E-cadherin, occludin, ZO-1 and integrin m RNA were positively related to the percentage of PCNA-positive cells.Conclusion： Weaning at 14 d of age induced damage to the intestinal morphology and barrier. While there was an adaptive restoration on d 7 post-weaning, the measured values did not return to the pre-weaning levels, which reflected the impairment of intercellular junctions and Kv channels.展开更多
Ion channels modulate cellular excitability by regulating ionic fluxes across biological membranes.Pathogenic mutations in ion channel genes give rise to epileptic disorders that are among the most frequent neurologic...Ion channels modulate cellular excitability by regulating ionic fluxes across biological membranes.Pathogenic mutations in ion channel genes give rise to epileptic disorders that are among the most frequent neurological diseases affecting millions of individuals worldwide.Epilepsies are trigge red by an imbalance between excitatory and inhibitory conductances.However,pathogenic mutations in the same allele can give rise to loss-of-function and/or gain-of-function va riants,all able to trigger epilepsy.Furthermore,certain alleles are associated with brain malformations even in the absence of a clear electrical phenotype.This body of evidence argues that the underlying epileptogenic mechanisms of ion channels are more diverse than originally thought.Studies focusing on ion channels in prenatal cortical development have shed light on this apparent paradox.The picture that emerges is that ion channels play crucial roles in landmark neurodevelopmental processes,including neuronal migration,neurite outgrowth,and synapse formation.Thus,pathogenic channel mutants can not only cause epileptic disorders by alte ring excitability,but further,by inducing morphological and synaptic abnormalities that are initiated during neocortex formation and may persist into the adult brain.展开更多
Fibromyalgia is characterized by the primary symptomsof persistent diffuse pain, fatigue, sleep disturbance and cognitive dysfunction. Persistent pain conditions, such as fibromyalgia, are often refractory to current ...Fibromyalgia is characterized by the primary symptomsof persistent diffuse pain, fatigue, sleep disturbance and cognitive dysfunction. Persistent pain conditions, such as fibromyalgia, are often refractory to current available therapies. An involvement of K^+ channels in the pathophysiology of fibromyalgia is emerging and supported by drug treatments for this condition exhibiting action at these molecular processes. K^+ channels constitute potential novel target candidates for pain therapy offering peripheral and/or central actions. The Kv7 channel activators, flupirtine and retigabine, have exhibited pharmacological profiles compatible to the requirements needed for use as a therapeutic approach to fibromyalgia. Clinical trials to address the multidimensional challenges of fibromyalgia with flupirtine and retigabine will provide important insight to the role of K^+ channels in this condition.展开更多
Objective: A variety of ion channels have been implicated in breast cancer proliferation and metastasis.Voltagegated K+(Kv) channels not only cause repolarization in excitable cells,but are also involved in multiple c...Objective: A variety of ion channels have been implicated in breast cancer proliferation and metastasis.Voltagegated K+(Kv) channels not only cause repolarization in excitable cells,but are also involved in multiple cellular functions in non-excitable cells.In this study we investigated the role of Kv channels in migration of BT474 breast cancer cells.Methods: Transwell technique was used to separate migratory cells from non-migratory ones and these two groups of cells were subject to electrophysiological examinations and microfluorimetric measurements for cytosolic Ca.Cell migration was examined in the absence or presence of Kv channel blockers.Results: When compared with non-migratory cells,migratory cells had much higher Kv current densities,but rather unexpectedly,more depolarized membrane potential and reduced Cainflux.Reverse transcriptasepolymerase chain reaction(RT-PCR) analysis revealed the presence of Kv1.1,Kv1.3,Kv1.5,Kv2.1,Kv3.3,Kv3.4 and Kv4.3 channels.Cell migration was markedly inhibited by tetraethylammonium(TEA),a delayed rectifier Kv channel blocker,but not by 4-aminopyridine,an A-type Kv channel blocker.Conclusions: Taken together,our results show that increased Kv channel expression played a role in BT474 cell migration,and Kv channels could be considered as biomarkers or potential therapeutic targets for breast cancer metastasis.The mechanism(s) by which Kv channels enhanced migration appeared unrelated to membrane hyperpolarization and Cainflux.展开更多
基金funded by the National Key Basic Research Program of China(2013CB127302)National Natural Science Foundation of China(31330075,31372326,31301988,31301989)+4 种基金the State Key Laboratory of Animal Nutrition(2004DA125184F1401)the Spark Program of Jiangxi Province(20142BBF061051)Changsha Lvye Biotechnology Limited Company Academician Expert WorkstationGuangdong Wangda Group Academician Workstation for Clean Feed Technology Research and Development in SwineGuangdong Hinapharm Group Academician Workstation for Biological Feed and Feed Additives and Animal Intestinal Health
文摘Background： The intestinal epithelium is an important barrier that depends on a complex mixture of proteins and these proteins comprise different intercellular junctions. The purpose of this study was to investigate the postnatal and developmental changes in morphology, intercellular junctions and voltage-gated potassium（Kv） channels in the intestine of piglets during the suckling and post-weaning periods.Results： Samples of the small intestine were obtained from 1-, 7-, 14-, and 21-d-old suckling piglets and piglets on d 1, 3, 5, and 7 after weaning at 14 d of age. The results showed that the percentage of proliferating cell nuclear antigen（PCNA）-positive cells and alkaline phosphatase（AKP） activity, as well as the abundances of E-cadherin,occludin, and Kv1.5 m RNA and claudin-1, claudin-3, and occludin protein in the jejunum were increased from d 1to d 21 during the suckling period（P 〈 0.05）. Weaning induced decreases in the percentage of PCNA-positive cells,AKP activity and the abundances of E-cadherin, occludin and zonula occludens（ZO）-1 m RNA or protein in the jejunum on d 1, 3 and 5 post-weaning（P 〈 0.05）. There were lower abundances of E-cadherin, occludin and ZO-1m RNA as well as claudin-1, claudin-3 and ZO-1 protein in the jejunum of weanling piglets than in 21-d-old suckling piglets（P 〈 0.05）. The abundances of E-cadherin, occludin, ZO-1 and integrin m RNA were positively related to the percentage of PCNA-positive cells.Conclusion： Weaning at 14 d of age induced damage to the intestinal morphology and barrier. While there was an adaptive restoration on d 7 post-weaning, the measured values did not return to the pre-weaning levels, which reflected the impairment of intercellular junctions and Kv channels.
基金NJ Governor’s Council for Medical Research and Treatment of Autism predoctoral fellowship (CAUT23AFP015) to ABNational Science Foundation grant (2030348) to FS。
文摘Ion channels modulate cellular excitability by regulating ionic fluxes across biological membranes.Pathogenic mutations in ion channel genes give rise to epileptic disorders that are among the most frequent neurological diseases affecting millions of individuals worldwide.Epilepsies are trigge red by an imbalance between excitatory and inhibitory conductances.However,pathogenic mutations in the same allele can give rise to loss-of-function and/or gain-of-function va riants,all able to trigger epilepsy.Furthermore,certain alleles are associated with brain malformations even in the absence of a clear electrical phenotype.This body of evidence argues that the underlying epileptogenic mechanisms of ion channels are more diverse than originally thought.Studies focusing on ion channels in prenatal cortical development have shed light on this apparent paradox.The picture that emerges is that ion channels play crucial roles in landmark neurodevelopmental processes,including neuronal migration,neurite outgrowth,and synapse formation.Thus,pathogenic channel mutants can not only cause epileptic disorders by alte ring excitability,but further,by inducing morphological and synaptic abnormalities that are initiated during neocortex formation and may persist into the adult brain.
文摘Fibromyalgia is characterized by the primary symptomsof persistent diffuse pain, fatigue, sleep disturbance and cognitive dysfunction. Persistent pain conditions, such as fibromyalgia, are often refractory to current available therapies. An involvement of K^+ channels in the pathophysiology of fibromyalgia is emerging and supported by drug treatments for this condition exhibiting action at these molecular processes. K^+ channels constitute potential novel target candidates for pain therapy offering peripheral and/or central actions. The Kv7 channel activators, flupirtine and retigabine, have exhibited pharmacological profiles compatible to the requirements needed for use as a therapeutic approach to fibromyalgia. Clinical trials to address the multidimensional challenges of fibromyalgia with flupirtine and retigabine will provide important insight to the role of K^+ channels in this condition.
基金funded by the Macao Science and Technology Development Fund(FUNDO PARA O DESENVOLVIMENTO DAS CIêNCIAS E DA TECNOLOGIA)and the reference number was 002/2015/A1
文摘Objective: A variety of ion channels have been implicated in breast cancer proliferation and metastasis.Voltagegated K+(Kv) channels not only cause repolarization in excitable cells,but are also involved in multiple cellular functions in non-excitable cells.In this study we investigated the role of Kv channels in migration of BT474 breast cancer cells.Methods: Transwell technique was used to separate migratory cells from non-migratory ones and these two groups of cells were subject to electrophysiological examinations and microfluorimetric measurements for cytosolic Ca.Cell migration was examined in the absence or presence of Kv channel blockers.Results: When compared with non-migratory cells,migratory cells had much higher Kv current densities,but rather unexpectedly,more depolarized membrane potential and reduced Cainflux.Reverse transcriptasepolymerase chain reaction(RT-PCR) analysis revealed the presence of Kv1.1,Kv1.3,Kv1.5,Kv2.1,Kv3.3,Kv3.4 and Kv4.3 channels.Cell migration was markedly inhibited by tetraethylammonium(TEA),a delayed rectifier Kv channel blocker,but not by 4-aminopyridine,an A-type Kv channel blocker.Conclusions: Taken together,our results show that increased Kv channel expression played a role in BT474 cell migration,and Kv channels could be considered as biomarkers or potential therapeutic targets for breast cancer metastasis.The mechanism(s) by which Kv channels enhanced migration appeared unrelated to membrane hyperpolarization and Cainflux.
