Aims T-type Ca<sup>2+</sup> current(I<sub>CaT</sub>)plays an important role in the pathogenesis of atrial fibrillation（AF）.The present study sought to investigate the role of Macrophage migra...Aims T-type Ca<sup>2+</sup> current(I<sub>CaT</sub>)plays an important role in the pathogenesis of atrial fibrillation（AF）.The present study sought to investigate the role of Macrophage migration inhibitory factor（MIF）,a pleiotropic cytokine,in the regulation of T-type Ca<sup>2+</sup> channel in atrium myocytes.Methods We used whole-cell voltage-clamp technique and biochemical assays to study the regulation and expression of I<sub>Ca</sub>,T in mouse atrium myocytes（HL-1 cells）.Results Serum MIF concentrations was slightly increased in patients with AF compared to sinus rhythm（SR） controls.In cultured HL-1 cells, significant amounts of MIF were produced in response to hydrogen peroxide（H<sub>2</sub>O<sub>2</sub>）,but not AngiotensinⅡ（AngⅡ）. Mouse recombinant MIF（rMIF）（20 or 40 nM,24 h） suppressed peak ICa,T by-38%and-60%in a concentration-dependent manner,impaired the voltage-dependent activation of I<sub>Ca</sub>,T,and down-regulated of TCC alG mRNA.Src inhibitors genistein and PPl significantly enhanced ICaT.The depression of ICa,T induced by rMIF could be reversed by genistein and PP1.Conclusions MIFis involved in the pathogenesis of AF,probably by decreasing ICa,T through impairment of the channel function and activation of c-Src kinases in atrium myocytes.展开更多
文摘Aims T-type Ca<sup>2+</sup> current(I<sub>CaT</sub>)plays an important role in the pathogenesis of atrial fibrillation（AF）.The present study sought to investigate the role of Macrophage migration inhibitory factor（MIF）,a pleiotropic cytokine,in the regulation of T-type Ca<sup>2+</sup> channel in atrium myocytes.Methods We used whole-cell voltage-clamp technique and biochemical assays to study the regulation and expression of I<sub>Ca</sub>,T in mouse atrium myocytes（HL-1 cells）.Results Serum MIF concentrations was slightly increased in patients with AF compared to sinus rhythm（SR） controls.In cultured HL-1 cells, significant amounts of MIF were produced in response to hydrogen peroxide（H<sub>2</sub>O<sub>2</sub>）,but not AngiotensinⅡ（AngⅡ）. Mouse recombinant MIF（rMIF）（20 or 40 nM,24 h） suppressed peak ICa,T by-38%and-60%in a concentration-dependent manner,impaired the voltage-dependent activation of I<sub>Ca</sub>,T,and down-regulated of TCC alG mRNA.Src inhibitors genistein and PPl significantly enhanced ICaT.The depression of ICa,T induced by rMIF could be reversed by genistein and PP1.Conclusions MIFis involved in the pathogenesis of AF,probably by decreasing ICa,T through impairment of the channel function and activation of c-Src kinases in atrium myocytes.
