title: Ionic mechanisms of the depression of automaticity and conduction in the rabbit atrioventricular node caused by hypoxia or metabolic inhibition and protective action of glucose and valine.
abstract: The effects of hypoxia and a metabolic inhibitor, sodium cyanide (NaCN), on the spontaneous action potential and membrane current systems were studied in small preparations (0.2 x 0.2 x 0.1 mm) of rabbit atrioventricular node. When the PO2 of the superfusate was lowered from 500 to less than 20 mm Hg, all the preparations initially showed reductions in the spontaneous firing frequency (due to the decreased rate of diastolic depolarization) and maximal rate of depolarization, which were followed by a cessation of automatic activity with subsequent membrane hyperpolarization to -57 +/- 3 mV (n = 4). Voltage clamp experiments using double microelectrode techniques revealed that hypoxia reduced the slow inward current by 20 to 80% without affecting its inactivation kinetics. The delayed rectifying potassium current tail was also reduced or abolished by severe hypoxia, whereas the background outward current was greatly increased. The hyperpolarization-activated inward current was decreased by hypoxia. Similar changes in the spontaneous action potential and membrane currents were obtained on adding 0.1 to 0.5 mM NaCN to the superfusate under conditions of normal PO2. Hypoxia-induced suppression of automaticity was reversed completely by 5 mM glucose, and partially by 40 mM valine. These results suggest that (1) hypoxia impairs atrioventricular nodal conduction by reducing the slow inward current and the delayed rectifying potassium current; (2) hypoxia depresses automaticity by increasing the background outward current and, to some extent, by reducing the slow inward current; and (3) glucose and valine contribute to the generation of high-energy phosphates in cytoplasm and mitochondria, respectively, and protect the atrioventricular node from hypoxia.
authors: Cardiovascular Institute, Fujita Gakuen Health University School of Medicine, Aichi, Japan.
authors: M
authors: M
authors: Nishimura
authors: H
authors: H
authors: Tanaka
authors: N
authors: N
authors: Homma
authors: T
authors: T
authors: Matsuzawa
authors: Y
authors: Y
authors: Watanabe
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001283:Atrioventricular Node / Q000503:physiopathology*; D001696:Biomechanical Phenomena; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D006329:Heart Conduction System / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D007473:Ion Channels / Q000502:physiology; D007477:Ions; D007930:Leucine / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009431:Neural Conduction; D011817:Rabbits; D012966:Sodium Cyanide / Q000494:pharmacology; D014633:Valine / Q000494:pharmacology*
chemical_list: D007473:Ion Channels; D007477:Ions; D007930:Leucine; D014633:Valine; D005947:Glucose; D012966:Sodium Cyanide