巨噬细胞移动抑制因子对HL-1细胞T型钙电流的调控

目的 观察巨噬细胞移动抑制因子（macrophage migration inhibitory factor,MIF）对心房肌细胞T型钙电流（T-type calcium channel current,ICa,T）的调控.方法 使用全细胞膜片钳和分子生物分析方法检测心房肌细胞ICa,T的表达.结果 在体外培养的心房肌细胞株（HL-1细胞）中,小鼠重组MIF（20、40 nmol/L,24 h）可明显抑制ICa,T的峰值电流,与对照组比较,差异均有统计学意义[峰值内向电流：（-17.5±2.9）pA/pF vs.（-27.9±3.4） pA/pF,P＜0.05;（-11.3±1.7）pA/pF vs.（-27.9±3.4）pA/pF,P＜0.01]；并可损伤电压依赖的ICa,T激活,使T型钙通道α1G和α1H亚单位mRNA表达下调.而Src非特异性抑制剂genistein和特异性抑制剂PP1可逆转40 nmol/L MIF所致的ICa,T下调[genistein：（-11.3±1.7）pA/pF vs.（-16.1±0.8）,P＜0.05；PPI：（-11.3±1.7）pA/pFvs.（-19.0±3.2）pA/pF,P＜0.05].结论 MIF可能通过影响ICa,T参与心房颤动的病理过程,Src可能参与该信号转导途径.

Regulation of macrophage migration inhibitory factor on T-type calcium channels in HL-1 cells

Objectives To investigate the role of macrophage migration inhibitory factor （MIF） in the regulation of Ttype calcium channels （Ica,T） in atrial myocytes.Methods The whole-cell voltage-clamp technique and biochemical assays were used to detect the regulation of ICa,T in atrial myocytes.Results In atrium-derived myocytes （HL-1 cells） cultured in vitro,mouse recombinant MIF （20 or 40 nmol/L,24 h） could significantly suppress peak ICa,T when compared with control group [（-17.5±2.9） pA/pF vs.（-27.9±3.4） pA/pF,P〈0.05; （-11.3±1.7） pA/pF vs.（-27.9±3.4）pA/pF,P〈0.01],impair the voltage-dependent activation of ICa,T and down-regulate the expressions of α1G and α1H mRNA of T-type calcium channels.The reduction of ICa,T induced by 40 nmol/L recombinant MIF could be reversed by genistein and PP1 [genistein：（-11.3±1.7） pA/pF vs.（-16.1±0.8）,P〈0.05; PPI：（-11.3±1.7） pA/pF vs.（-19.0±3.2） pA/pF,P〈0.05].Conclusions MIF may be involved in the pathogenesis of atrial fibrillation by affecting the ICa,T in atrium-derived myocytes,in which Src may take part in the signal transduction pathway.