J4 ›› 2012, Vol. 38 ›› Issue (5): 845-849.

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Differential regulation of Kv1.3 and Kir2.1 expression by gemfibrozil in human macrophages and its effects on their membrane potentials

LEI Xin-jun1,ZHANG Wei2,LIN Xian-feng3,WANG Dong-qi1,YUAN Zu-yi1,4   

  1. (1.Department of Cardiology,First Affiliated Hospital| College of Medicine,Xi’an Jiaotong University,Xi’an 710061,China|2.Department of Pediatrics,First Affiliated Hospital, College of Medicine, Xi’an Jiaotong University,Xi’an 710061,China; |3.Krannert Institute of Cardiology and Division of Cardiology,School of Medicine,Indiana University,IN 46202, USA|4.Key Laborato of Environment and Gene Related to Diseases,Ministry of Education,Xi’an Jiaotong University,Xi’an 710061,China)
  • Received:2012-07-06 Online:2012-09-28 Published:2012-09-28

Abstract:

Abstract:Objective
 To explore the development change of Kv1.3 and Kir2.1 channels in human macrophages and the effects of gemfibrozil on both channels’ expression and their membrane potentials,which will provide electrophysiologic basis for its treating atherosclerotic diseases.Methods The obtained human monocyte-derived macrophages were randomly divided into 3 groups: control 5 d group (C 5d),control 7.5 d group (C 7.5d) and gemfibrozil group (G).The final concentration of gemfibrozil was 400  μmo•L-1.The effect of gemfibrozil on the expressions of Kv1.3 and Kir2.1 channels was investigated using Real time RT-PCR and Western blotting,and its effect on membrane potentials was analyzed with the optical mapping of the membrane potential with the voltage-sensitive dyes. Results  Compared with  C 5d group,the expressions of Kv1.3 mRNA/protein in  C 7.5d group were raised from (1.064±0.275)/(0.227±0.018) to (3.067±0.824)/(0.409±0.022) (P<0.05),but the expressions of Kir2.1 mRNA/protein were decreased from (1.024±0.166)/(0.204±0.018) to (0.399±0.133)/(0.042±0.008)(P<0.05). Compared with  C 7.5d group,the expressions of Kv1.3 mRNA/protein in  gemfibrozil group were reduced to (1.137±0.067)/(0.143±0.023) (P<0.01); however,the expressions of Kir2.1 mRNA/protein were elevated to (1.35±0.087)/(0.202±0.033)(P<0.01).Meanwhile,gemfibrozil significantly reduced the surface fluorescence intensity of the macrophages,and the membrane potentials in  C 5d and C 7.5d groups were decreased from (1.000±0.026) to (0.833±0.046) and (0.481±0.053),respectively (P<0.05).Conclusion Gemfibrozil differentially regulates the expressions of Kv1.3 and Kir2.1 channels in human monocyte-derived macrophages,
and lowered their membrane potentials.

Key words: ionic channel, membrane potential, macrophage, gemfibrozil, cell differentiation

CLC Number: 

  • R363.21