Effects of 3,3′,4,4′,5-pentachlorobiphenyl on human Kv1.3 and Kv1.5 channels

Among the environmental chemicals that may be able to disrupt the endocrine systems of animals and humans are polychlorinated biphenyls (PCBs), a chemical class of considerable concern. PCB consists of two six-carbon rings linked by a single carbon bond, and theoretically, 209 congeners can form, depending on the number of chlorines and their location on the biphenyl rings. Furthermore, 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) exposure also increases nitric oxide production and nuclear factor kappa-light-chain-enhancer of activated B cells binding activity in chondrocytes, thus contributing as an initiator of chondrocyte apoptosis and resulting in thymic atrophy and immunosuppression. This study identified whether cardiac and immune abnormalities from PCB126 were caused by the Kv1.3 and Kv1.5 channels. PCB126 did not affect either the steady-state current or peak current of the Kv1.3 and Kv1.5 channels. However, PCB126 right-shifted the steady-state activation curves of human Kv1.3 channels. These results suggest that PCBs can affect the heart in a way that does not block voltage-dependent potassium channels including Kv1.3 and Kv1.5 directly.

Antagonization of eplerenone on proliferation of cardiac fibroblasts induced by co-cultured Treg cells based on inhibition of Kv1.3 channel of Tregs / 中国药理学通报

Aim To establish a co-incubation system in cardiac fibroblasts of SD neonatal rats and spleen CD4+ CD25 + regulatory T lymphocytes (Tregs) of normal adult SD rats,and to investigate the effects of eplerenone(EPL) on the interaction of two cells and the relationship with the Kvl.3 channel on Tregs cell membrane.Methods The spleen Tregs of normal adult SD rats were sorted by immunomagnetic bead sorting,and the myocardial fibroblasts of SD rats were isolated by differential adherence method.The experiment was conducted in the following groups:CFs,CFs + Tregs,CFs + Tregs + EPL,Tregs.The proliferation of CFs was detected by CCK-8 method.The expression levels of type Ⅰ collagen,type m collagen and matrix metalloproteinase 2 (MMP-2) secreted by CFs were detected by ELISA.The mRNA expression levels of Kv1.3,KCa3.1 on Tregs cell membrane and intracellular CRAC channel were detected by RT-qPCR technique.Tregs cell membrane Kvl.3 channel protein expression levels were determined by In-Cell Western blot.Results After 48 h incubation of the co-culture system,the cell proliferation was stable.CFs proliferation was marked(P ＜0.01),which could be inhibited by EPL(P ＜0.01).The type Ⅰ,type Ⅲ collagen and MMP-2 secreted by CFs increased (P ＜ 0.01).The expression levels of Kv1.3,KCa3.1 and CRAC channel mRNA in Tregs increased by 6.95,1.99 and 1.53 fold (CFs + Tregs vs Tregs,P ＜0.01),EPL decreased the mRNA level of each channel (CFs +Tregs + EPLvs CFs + Tregs,P＜0.01),and the decrease of Kv1.3 channel was the most significant (P ＜ 0.01).The Kv1.3 channel protein of Tregs increased by 67.9％ (CFs + Tregs vs Tregs,P ＜0.01),which could be inhibited by EPL(P ＜ 0.01).Conclusions Tregs cultured with CFs after 48 h can significantly promote the proliferation of CFs,and EPL can down-regulate the Kv1.3 channel expression on the Tregs membrane and inhibit the activation/proliferation of Tregs,indirectly inhibiting myocardial fibrosis.

Kv1.3 channel current changes in neutrophilic asthma and eosinophilic asthma / 国际儿科学杂志

Objective Allergic asthma is a chronic inflammatory disease of the airways.T lymphocytes play important roles in the pathogenesis of asthma.The voltage-gated Kvl.3 potassium channel may be a key factor in the activation of T lymphocytes.This research aims to detect the function of Kvl.3 channel in the neutrophlial asthma(NA) model and eosinophilic asthma(EA) model.Methods A total of 24 mice were randomly assigned into three groups:control,neutrophilic asthma model and eosinophilic asthma group.Neutrophilic asthma model was established with ovalbumin (OVA)and lipopolysaccharide(LPS);eosinophilic asthma was established with OVA and Al(OH)3;airway responsiveness of mice in each group was measured with a noninvasive pulmonary function instrument;lung inflammation changes were observed by pathological HE staining;IL-17A and IL-4 cytokines levels in bronchoalveolar lavage fluid were evaluated by ELISA;Kvl.3 channel protein level in lung was evaluated by western blot;the change of current density in CD4 +.T lymphocytes were tested by whole-cell patch clamp technique.Results Levels of IL-17A and IL-4 in bronchoalveolar lavage fluid increased in both NA and EA model (P ＜ 0.05).Compare with EA model,the IL-17A level was significantly higer in NA model,while the IL-4 level was significantly lower.In NA and EA model,kv1.3 protein expression in lung tissue was significantly higher than that in the control group(P ＜ 0.05),and kv1.3 protein expression in NA model was significantly higer than that in the EA model (P ＜ 0.05).Current intensity and current density of kv1.3 channel increased in both NA and EA model.While the current intensity and current density of kv1.3 channel were significantly higher in NA model than that in EA model.Conclusion Kv1.3 protein level,Kv1.3 channel current intensity and kv1.3 channel current density increased in both NA and EA model,especially in NA group,providing a new way for treatment of bronchial asthma.