MODULATION OF CARDIAC NA+-K+ PUMP CURRENT - ROLE OF PROTEIN AND NONPROTEIN SULFHYDRYL REDOX STATUS

被引:33
作者
HADDOCK, PS [1 ]
SHATTOCK, MJ [1 ]
HEARSE, DJ [1 ]
机构
[1] ST THOMAS HOSP, RAYNE INST, LONDON SE1 7EH, ENGLAND
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 1995年 / 269卷 / 01期
基金
英国惠康基金;
关键词
GLUTATHIONE; PROTEIN SULFHYDRYL GROUPS; S-THIOLATION; ISCHEMIA;
D O I
10.1152/ajpheart.1995.269.1.H297
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Oxidant stress alters protein structure and function, possibly through the modification of the redox status of regulatory protein sulfhydryl groups. We used the sulfhydryl-blocking reagent p-chloromercuriphenylsulfonic acid (pCMPSA), applied selectively and independently to either the intracellular or extracellular environment, to study the relationship between blocking protein sulfhydryl groups and Na+-K+ pump current (i(p)). In guinea pig ventricular myocytes voltage clamped at -30 mV, extracellular pCMPSA (50, 100, and 400 mu M) caused a concentration-dependent reduction in holding current. The selective intracellular administration of pCMPSA (100 mu M) induced a similar inhibition of i(p), albeit over a longer time course. The inhibition of i(p) resulting from either the intracellular or extracellular application of pCMPSA (100 mu M) was reversed, in part, by the extracellular application of dithiothreitol (3 mM). An intracellular oxidant stress was also imposed by using diethyl maleate to deplete the intracellular nonprotein sulfhydryl content [represented by reduced glutathione (GSH)]. In myocytes isolated from diethyl maleate-treated guinea pigs (860 mg/kg ip, 30 min before study), intracellular GSH was depleted by 93% and i(p) was depressed by 38% at all membrane potentials tested. We propose that Na+-K+ pump function may be related to protein and nonprotein sulfhydryl status. Protein sulfhydryl oxidation and glutathione depletion may account, in part, for a depression in Na+-K+ pump activity during reperfusion-induced oxidant stress.
引用
收藏
页码:H297 / H307
页数:11
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