[Nitric oxide increases persistent sodium current of ventricular myocytes in guinea pig during normoxia and hypoxia].
Whole cell patch-clamp technique was used to record the changes of persistent sodium current (I(Na.P)) and the effect of administered agents in ventricular myocytes of guinea pig to investigate the essence of I(Na.P) and mechanism of increased I(Na.P) of ventricular myocytes during hypoxia. The results showed: (1) Pro-NO L-arginine(L-Arg) and donor sodium nitroprusside (SNP) increased I(Na.P) in a concentration-dependent manner in normoxia. (2) I(Na.P) increased gradually with the prolongation of hypoxia time. After 15 min of hypoxia, administration of N(G)-nitro-L-arginine methyl ester (L-NAME), a NO synthase inhibitor, could not significantly recover the increased I(Na.P) [(1.344+/-0.320) vs (1.301+/-0.317) pA/pF, P>0.05, n=5]; (3) During hypoxia the perfusion solution with L-NAME decreased the increased I(Na.P), and the difference was significant compared with pure hypoxia [(0.914+/-0.263), n=5 vs (1.344+/-0.320) pA/pF, P<0.05, n=6], whereas the amplitude of I(Na.P) was still larger than that in normoxia [(0.914+/-0.263) vs (0.497+/-0.149) pA/pF, P<0.05, n=5]; (4) Reducing agent dithiothreitiol (DTT) not only recovered the increased I(Na.P) by L-Arg and administered SNP after hypoxia [(1.449+/-0.522) vs (0.414+/-0.067) pA/pF, P<0.01, n=6, and (1.786+/-0.636) vs (0.436+/-0.141) pA/pF, P<0.01, n=5, respectively], but also decreased the I(Na.P) in normoxia [(0.442+/-0.056) vs (0.396+/-0.057) pA/pF, P<0.01, n=6]. Our results suggest that hypoxia increases I(Na.P) of ventricular myocytes, which is induced by raised NO oxidating sodium channel protein in myocardial membrane during hypoxia. The activity of I(Na.P) in normoxia is related to the oxidation state of the channel protein.
Ma
Ji-Hua
JH
Cardio-Electrophysiological Research Laboratory, Medical College, Wuhan University of Science and Technology, China. mjhua@wust.edu.cn
Wang
Xian-Pei
XP
Zhang
Pei-Hua
PH
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D002469:Cell Separation; D005260:Female; D006168:Guinea Pigs; D006352:Heart Ventricles; D008297:Male; D009206:Myocardium / Q000166:cytology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D015222:Sodium Channels / Q000502:physiology*
D015222:Sodium Channels; D009599:Nitroprusside; D009569:Nitric Oxide