Large conductance calcium-activated potassium （BKca） channels are broadly expressed in vascular smooth muscle cells （VSMCs） and play a crucial role in the regulation of vascular tone.
Xiuli ChengXiaoqiu TanWeixia LiuHui LiLi YanYan YangXiaorong ZengJimin Cao
This study aimed to comprehend the largely unknown role of voltage-gated potassium channel 1.3 （Kvl.3） in the phagocytic function of macrophages. We found that blocking of the Kv 1.3 channel with 100 pmol L 1 Stichodactyla helianthus neurotoxin （ShK） enhanced the phagocytic capacities of both resting and lipopolysaccharide （LPS）-stimulated RAW264.7 macrophages in the chicken erythrocyte system. In the fluorescein isothiocyanate （FITC）-labeled Escherichia coli k-12 system, ShK increased the phagocytic capacities of resting RAW264.7 cells, but not of the LPS-stimulated cells, as LPS alone stimulated almost satu- rated phagocytosis of the macrophages. ShK increased the nitric oxide （NO） production in LPS-activated cells, but not in rest- ing RAW264.7 cells. There was no effect of ShK alone on the cytokine secretions in resting RAW264.7 cells, but it suppressed IL-113 secretion in LPS-stimulated RAW264.7 cells. At a concentration of 100 pmol L 1, ShK did not affect the viability of the tested cells. Kv 1.3 was expressed in RAW264.7 cells; this expression was downregulated by LPS, but significantly upregulat- ed by disrupting caveolin-dependent endocytosis with filipin III. In addition, cytochalasin D, an inhibitor of actin polymeriza- tion, did not affect the Kvl.3 expression. Thus, blocking of the Kvl.3 channel enhances the phagocytic capacity and NO pro- duction of this cell line. Our results suggest that Kv 1.3 channel serves as a negative regulator of phagocytosis in macrophages and can therefore be a potential target in the treatment of macrophage dysfunction.
Autoimmune activities have been implicated in the pathogenesis of hypertension.High levels of autoantibodies against the second extracellular loop of α1-adrenoceptor(α1-AR autoantibody,α1-AA) are found in patients with hypertension,and α1-AA could exert a α1-AR agonist-like vasoconstrictive effect.However,whether the vasoconstrictive effect of α1-AA is enhanced in hypertension is unknown.Using aortic rings of spontaneously hypertensive rats(SHR) and normotensive Wistar-Kyoto(WKY) rats,we observed the vasoconstrictive responses to α1-AA with phenylephrine(α1-AR agonist) as a positive control drug.Aortic nitrotyrosine levels were also measured by ELISA and immunohistochemistry.The results showed that the aortic constrictive responses to α1-AA and phenylephrine(both 1 nmol L-1-10 μmol L-1) were greater in SHR than in WKY rats.Endothelial denudation or L-NAME(a non-selective NOS inhibitor)(100 μmol L-1) increased α1-AA- or phenylephrine-induced vasoconstrictions both in SHR and WKY.However,selective iNOS inhibitor 1400W(10 μmol L-1) enhanced the α1-AA-induced aortic constriction in WKY,but not in SHR.The aortic nitrotyrosine level was significantly higher in SHR than WKY,as shown by both ELISA and immunohistochemistry.These results indicate that the vasoconstrictive response to α1-AA is enhanced in SHR,and this altered responsiveness is due to endothelial dysfunction and decreased NO bioavailability.The study suggests an important role of α1-AR autoimmunity in the pathogenesis and management of hypertension especially in those harboring high α1-AA levels.
YAN LiTAN XiaoQiuCHEN WenXuanZHU HongCAO JiMinLIU HuiRong
