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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

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

Qiong Tang, Jihua Ma, Peihua Zhang, Wei Wan, Linghao Kong, Lin Wu

Pflugers Arch. 2012 Apr;463(4):513-22.

PMID: 22234427

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP852146737	KR-32568		852146-73-7	Price

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