title: Persistent sodium current and Na+/H+ exchange contributes to the augmentation of the reverse Na+/Ca2+ exchange during hypoxia or acute ischemia in ventricular myocytes.
abstract: The increases in persistent sodium currents (I                         (Na.P)) and Na(+)/H(+) exchange (NHE) causes intracellular Ca(2+) overload. The objective of this study was to determine the contribution of I                         (Na.P) and NHE on the hypoxia- or acute ischemia-induced increase in the reverse Na(+)/Ca(2+) exchange current (HIR- or AIR-I                         (NCX)). I                         (Na.P) and I                         (NCX) in rabbit ventricular myocytes were recorded during hypoxia or acute ischemia, combination of acidosis (pH values were 6.0 intracellularly and 6.8 extracellularly) and hypoxia, using whole-cell patch-clamp techniques. The results indicate that (1) under hypoxic condition, the augmentation of both HIR-I                         (NCX) and I                         (Na.P) was inhibited by TTX (2 to 8 μM) in a concentration-dependent manner. The inhibitions of I                         (Na,P) and HIR-I                         (NCX) reached maximum in the presence of either 4 μM TTX or 10 μM KR-32568 (a NHE inhibitor), respectively. The maximal inhibitions of HIR-I                         (NCX) by 4 μM TTX and 10 μM KR-32568 were 72.54% and 16.89%, respectively. (2) Administration of 2 μM TTX and 10 μM KR-32568 in either order in the same cells decreased HIR-I                         (NCX) by 64.83% and 16.94%, respectively. (3) I                         (Na.P) and the reverse I                         (NCX) were augmented during acute ischemia. TTX (4 μM) and KR-32568 (10 μM) reduced AIR-I                         (NCX) by 73.39% and 24.13%, respectively. (4) Under normoxic condition, veratridine (20 μM) significantly increased I                         (Na.P) and the reverse I                         (NCX), which was reversed by 4 μM TTX. In conclusion, during hypoxia or acute ischemia, both increased I                         (Na.P) and NHE contribute to the HIR- or AIR-I                         (NCX) with the former playing a major role comparing with the latter.
authors.affiliation: Cardio-Electrophysiological Research Laboratory, Medical College, Wuhan University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Tang
authors.forename: Jihua
authors.initials: J
authors.lastname: Ma
authors.forename: Peihua
authors.initials: P
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Wan
authors.forename: Linghao
authors.initials: L
authors.lastname: Kong
authors.forename: Lin
authors.initials: L
authors.lastname: Wu
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D004305:Dose-Response Relationship, Drug; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011817:Rabbits; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D006146:Guanidines; C507121:KR-32568; D019831:Sodium-Calcium Exchanger; D017923:Sodium-Hydrogen Exchangers; D013779:Tetrodotoxin