Effects of SO_(2)derivatives on sodium currents in acutely isolated rat hippocampal lead-exposed neurons

In this study, the effects of acute SO_2 derivatives and chronic lead exposure together on sodium cur-rents (INa) were investigated in acutely isolated rat hippocampal neurons by using the whole-cell patch clamp techniques. We found that chronic lead exposure hardly reduced the amplitudes of INa. In the normal condition, sodium current started to appear at around ?70 mV, and reached the peak current at around ?40 mV. After chronic lead exposure, the data changed to ?70 and ?30 mV. After adding SO2 derivatives, the data changed to ?80 and ?40 mV, respectively. SO_2 derivatives caused a significant in-crease of INa in hippocampal chronic-lead exposed neurons. Chronic lead exposure induced a right shift of the activation curve and a left shift of the inactivation curve of sodium channels. SO_2 derivatives caused negative shifts of the activation and inactivation curves of INa in hippocampal chronic-lead ex-posed neurons. Lead exposure put off the time reaching the peak of INa activation. SO_2 derivatives in-creased the time constants of inactivation after lead exposure. The interaction of lead and SO_2 deriva-tives with voltage-dependent sodium channels may lead to changes in electrical activity and contribute to worsening the neurotoxicological damage.

Regulation of cardiac hERG potassium channel by protein tyrosine phosphatase non-receptor type 12, 11 and 6

Background Long QT syndrome(LQTS)is a potentially fatal cardiac ion channel disease.Mutations in the gene encoding cardiac hERG potassium channel are the second most common causes of LQTS.Cardiac hERG potassium channel conducts the rapidly activating delayed rectifier potassium current(Ikr),which is one of the crucial currents in rapid repolarization phase of action potential in human cardiomyocytes.Function of hERG potassium channel is regulated by a variety of signaling pathways,in which phosphorylation and dephosphorylation of tyrosine proteins plays a major role.Previous research has found that non-receptor protein tyrosine phosphatase(PTPN)can interact with hERG potassium channel in cardiac cells.The aims of the present study were to investigate the regulatory effect of protein tyrosine phosphatase non-receptor type 12,11 and 6(PTPN12,PTPN11 and PTPN6)on cardiac hERG potassium channels.Methods HEK-293 cells were transfected with pcDNA3.0-hERG by Lipofectamine 2000 and selected by G418.HEK-293/hERG cells stably expressing hERG protein were then transfected with pcDNA3.1-PTPN12-RFP,pcDNA3.1-PTPN11-EGFP and pcDNA3.1-PTPN6-EGFP,respectively.Forty-eight hours after transfection,immunofluorescence assay and western blot were performed to detect the expression of hERG channel proteins and PTPN proteins.hERG channel currents in hERG alone-expressing group,PTPN12-,PTPN11-and PTPN6-overexpressing groups,as well as inhibitor groups were recorded by patch clamp technique.Results The maximum pulse current densities of PTPN12-,PTPN11-and PTPN6-overexpressing groups were all decreased when compared with hERG alone-expressing group(P<0.05).However,the maximum pulse current densities of inhibitor groups were all increased when compared with PTPN12-,PTPN11-and PTPN6-overexpressing groups,respectively(P<0.05).Conclusions Overexpression of PTPN12,PTPN11 and PTPN6 reduced the current density of hERG potassium channel,while this effect could be reversed by tyrosine phosphatase inhibitors.These results suggested that PTPN12,PTPN11 and PTPN6 negatively regulated hERG potassium channel currents by catalyzing the dephosphorylation process of hERG potassium channels.[S Chin J Cardiol 2021;22(1):38-49]