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Sulfhydryl modification affects coronary artery tension by changing activity of delayed rectifier K+ current.

 Miyong Ha  ;  SungChoon Kwon  ;  Young Ho Lee  ;  Dongsoo Yeon  ;  Duck Sun Ahn 
 Yonsei Medical Journal, Vol.41(3) : 372-380, 2000 
Journal Title
 Yonsei Medical Journal 
Issue Date
Animals ; Arteries/cytology ; Arteries/drug effects ; Arteries/physiology ; Coronary Vessels/cytology ; Coronary Vessels/drug effects* ; Coronary Vessels/physiology ; Delayed Rectifier Potassium Channels ; Female ; Male ; Oxidants/pharmacology* ; Potassium Channels/physiology ; Potassium Channels, Voltage-Gated* ; Rabbits ; Reducing Agents/pharmacology* ; Sulfhydryl Compounds/metabolism* ; Vasoconstriction/drug effects* ; Vasoconstriction/physiology
Coronary artery ; delayed rectifier K+ current ; diamide ; dithiothreitol ; glutathione ; redox
It has been reported that a change in the cellular redox state may be involved in the regulation of vascular tone, but the underlying mechanism is not fully understood. The present study was designed to investigate the cellular effect of sulfhydryl modifying agents in the coronary artery of rabbit using the tension measurement and whole cell clamping method. The application of diamide, a sulfhydryl oxidizing agent, relaxed the endothelium denuded coronary arteries in a dose dependent manner. The fact that this diamide-induced relaxation was significantly attenuated by a pretreatment of 4-AP, and the coronary arteries precontracted with 100 mM K+ instead of histamine, suggests the involvement of 4-AP sensitive K+ channels in the diamide-induced relaxation of coronary arteries. Whole cell patch clamp studies revealed that the 4-AP sensitive IdK was significantly enhanced by the membrane permeant oxidizing agents, diamide and DTDP, and were reversed by subsequent exposure to the reducing agent, DTT. Neither the membrane impermeant oxidizing or reducing agents, GSSG or GSH, had any effect on the activity of IdK, indicating that intracellular sulfhydryl modification is critical for modulating IdK activity. The Diamide failed to significantly alter the voltage dependence of the activation and inactivation parameters, and did not change the inactivation process, suggesting that diamide increases the number of functional channels without altering their gating properties. Since IdK has been believed to play an important role in regulating membrane potential and arterial tone, our results about the effect of sulfhydryl modifying agents on coronary arterial tone and IdK activity should help understand the pathophysiology of the diseases, where oxidative damage has been implicated.
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Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
Yonsei Authors
Ahn, Duk Sun(안덕선) ORCID logo https://orcid.org/0000-0001-9351-6951
Lee, Young Ho(이영호) ORCID logo https://orcid.org/0000-0002-5749-1045
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