Regulatory effect of protein tyrosine phosphatase non-receptor type on the cardiac Kv11.1 (HERG) potas-sium channel / 医学研究生学报

ABSTRACT

Objective Cardiac HERG potassium channel currents can cause long QT syndrome .The function of the cardiac HERG potassium channel is regulated by tyrosine kinase and phosphatase , and protein tyrosine phosphatase non-receptor type 11 ( PTPN11) negatively regulates the HERG potassium channel .This study aimed to investigate the effect of PTPN 11 on the electrophysio-logical characteristics of the HERG channel . Methods The plasmids of pcDNA3.1-PTPN11-EGFP were constructed by PCR technique and transfected or cotransfected with the pcDNA 3.1-PTPN11-EGFP plasmid into HEK293 cells using Lipofectamine 2000.The patch clamp technique was employed to record the HERG channel currents in the control group ( HEK293 cells transfected with pcDNA3.0-HERG-EGFP), PTPN11 overexpression group (pcDNA3.0-HERG and pcDNA3.1-PTPN6-EGFP cotransfected HEK293 cells), and PTPN11 overexpression with PAO group . Results The pcDNA3.1-PTPN11-EGFP plasmid was successfully constructed .Green fluorescence was observed in the HEK293 cells transfected with pcDNA3.0-HERG-EG-FP or cotransfected with pcDNA3.0-HERG and pcDNA3.1-PTPN11.The maximum densities of pulse and tail currents were significantly decreased in the PTPN11 overexpression group as compared with the control ([31.85 ±5.54] vs [45.92 ±3.18] pApF, P<0.05;[73.82 ±11.31] vs [108.43 ±7.98] pApF, P<0.05) but markedly in-creased in the PTPN11 overexpression with PAO group ([48.08 ±4.32] pApF;[120.06 ±8.02] pApF) (P<0.05).The time con-stant of deactivation was significantly higher in the PTPN 11 overexpression group than in the control ([622.16 ±46.49] vs [440.70 ± 49.49] ms, P<0.05). Conclusion The overexpression of PTPN11 decreases HERG potassium channel currents , which can be re-versed by PAO.This finding provides a theoretical basis for the application of certain regulatory enzymes in the HERG channel as a treat -ment of long QT syndrome .