title: Role for ATP-sensitive K+ channel in the development of A-V block during hypoxia.
abstract: The role of the ATP-sensitive K+ channel (IK,ATP) in the development of A-V block during hypoxic interventions was studied using Langendorff perfused rabbit hearts, multicellular rabbit A-V nodal preparations and single guinea-pig ventricular myocytes. With the Langendorff perfused hearts, hypoxic perfusion (PO2 not equal to 40 mmHg) for 30 min caused slowing of the sinus rate and prolongation of the A-H interval without the appearance of blocked beats. Substrate-free hypoxic perfusion induced second or third degree A-V block in 8/10 hearts and substrate-free hypoxic perfusion plus 2-deoxyglucose (5 mM) produced third degree A-V block in 6/6 preparations. Addition of 50 mM glucose in the perfusate restored A-V conduction during hypoxic intervention. Application of glibenclamide, a specific blocker of IK,ATP, prevented the development of second or third degree A-V block during substrate-free hypoxia (n = 6), whereas pinacidil, an opener of IK,ATP, caused development of third degree A-V block during hypoxia (n = 9). Application of theophylline (100 microM) or 8-phenyl-theophylline (10 microM) did not prevent the development of advanced degrees of A-V block during hypoxic interventions. In multicellular A-V nodal preparations, 10 microM glibenclamide prevented the shortening of action potential duration and block development without marked effects on the maximum upstroke velocity of action potentials during hypoxic intervention. In isolated ventricular myocytes studied by the patchclamp method, the substrate-free hypoxia plus 2-deoxyglucose induced the openings of IK,ATP in 9/25 preparations with cell-attached patches, while 2/20 patches exhibited sporadic channel openings in the normoxic condition during comparable observation period. These results suggest that openings of the ATP-sensitive K+ channels play a role in the development and aggravation of advanced A-V block during hypoxic interventions.
authors.affiliation: Department of Cardiovascular Diseases, Tokyo Medical and Dental University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sawanobori
authors.forename: H
authors.initials: H
authors.lastname: Adaniya
authors.forename: H
authors.initials: H
authors.lastname: Yukisada
authors.forename: M
authors.initials: M
authors.lastname: Hiraoka
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D003847:Deoxyglucose / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D006327:Heart Block / Q000503:physiopathology*; D000860:Hypoxia; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D010477:Perfusion; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors
chemical_list: D015221:Potassium Channels; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D013806:Theophylline; C028322:8-phenyltheophylline; D005947:Glucose; D005905:Glyburide