Potentiation by nitric oxide of the ATP‐sensitive K⁺ current induced by K⁺ channel openers in guinea‐pig ventricular cells

• Atsushi Shinbo

• Toshihiko Iijima

抄録

<jats:list list-type="explicit-label"> Modulation by nitric oxide (NO) of the ATP‐sensitive K + channel (K ATP ) current ( I K (ATP) ) was investigated in single ventricular cells dissociated from guinea‐pig hearts. I K (ATP) was induced by 5‐amino‐ N ‐[2‐(2‐chlorophenyl)ethyl]‐ N ′‐cyano‐3‐pyridinecarboxamidine (KRN4884) and cromakalim. In the whole‐cell patch clamp configuration, KRN4884 (0.13 μ m ) increased the outward current in a concentration‐dependent manner with an EC 50 value of 0.48 μ m . This current was completely antagonized by glibenclamide (1 μ m ). I K (ATP) induced by either KRN4884 (0.3 μ m ) or cromakalim (10 μ m ) was significantly enhanced by the additional application of a NO donor (±)‐(E)‐ethyl‐2‐[(E)‐hydroxyimino]‐5‐nitro‐3‐hexeneamide (NOR3, 0.1 and 1 m m ). The potentiating effect was observed only when NOR3 solution was prepared just before experiments, when release of NO was considered to be on‐going. The effect was significantly eliminated in the presence of the NO scavenger oxyhaemoglobin (310 μ m ). Also, oxidative metabolites of NO, such as NO 2 − or NO 3 − , were without effect. 8‐Bromo‐guanosine‐3′ : 5′‐cyclic monophosphate (8‐Br‐cyclic GMP, 0.10.5 m m ) significantly decreased I K (ATP) induced by KRN4884. In cell‐attached patches, NOR3 (1 m m ) potentiated the KRN4884‐induced I K (ATP) in a way similar to that seen in whole‐cell recordings. By contrast, NOR3 (1 m m ) did not enhance the current in either inside‐out or outside‐out patches. These results indicate that NO potentiates the action of K + channel openers on the K ATP through a mechanism which remains to be determined. British Journal of Pharmacology (1997) 120 , 1568–1574; doi:<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" xlink:href="10.1038/sj.bjp.0701069">10.1038/sj.bjp.0701069

収録刊行物

• British Journal of Pharmacology

  British Journal of Pharmacology 120 (8), 1568-1574, 1997-04

  Wiley

キーワード

• Pharmacology

詳細情報

• CRID: 1362544419833195136
• NII論文ID: 80009579613
• DOI: 10.1038/sj.bjp.0701069
• ISSN: 14765381
• ISSN: 00071188
• ISSN: http://id.crossref.org/issn/00071188
• Web Site: https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1038%2Fsj.bjp.0701069
• Web Site: https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1038/sj.bjp.0701069
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