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Role of PKG in the hypoxia‐induced activation of cardiac K ATP channels in goldfish
Author(s) -
Park Sarah D.,
Cameron John S.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a593-a
Subject(s) - cgmp dependent protein kinase , chelerythrine , nitric oxide , hypoxia (environmental) , atp sensitive potassium channel , protein kinase a , chemistry , medicine , soluble guanylyl cyclase , intracellular , potassium channel , protein kinase c , patch clamp , endocrinology , myocyte , electrophysiology , kinase , biology , biochemistry , glibenclamide , oxygen , cyclic gmp , mitogen activated protein kinase kinase , organic chemistry , diabetes mellitus
Previous data suggest a role for nitric oxide (NO) in the cardioprotective activation of sarcolemmal ATP‐sensitive potassium (K ATP ) channels in teleosts during moderate environmental hypoxia. Under low oxygen, K ATP channel opening is thought to involve NO‐sensitive guanylyl cyclase (GC) and a cGMP‐dependent pathway. The purpose this study was to assess the extent to which channel activation is further mediated by cGMP‐activated protein kinase (PKG) in the heart of the hypoxia‐tolerant goldfish ( Carassius auratus ). Intracellular and patch‐clamp recording techniques were used with excised ventricles or isolated ventricular myocytes, respectively. During moderate hypoxia (6–7 kPa), action potential duration (APD) was significantly reduced, a response that was mimicked by NO donors and by the potent cGMP analog 8‐pCPT‐cGMP (10 μM), but abolished by ODQ (10 μM), a specific inhibitor of NO‐sensitive GC. In cell‐attached membrane patches, the hypoxia‐induced activation of K ATP channels was blocked by ODQ but unaffected by selective inhibitors of cGMP‐activated PKG (KT‐5328; 0.5 μM) or of protein kinase C (chelerythrine; 5 μM). An increase in channel activity caused by 8‐pCPT‐cGMP was also not prevented by KT‐5328. Our data support a role for an NO‐cGMP‐dependent pathway in enhancing the sarcolemmal K ATP current during moderate hypoxia in this species, but suggest that the response is independent of PKG.