Effects of K+ channel blockers on the action potential of hypoxic rabbit myocardium.
1. In order to assess the role of different ionic currents in hypoxia-induced action potential shortening, we investigated the effects of blockers of voltage-dependent and ATP-sensitive K(+)-channel on the membrane potential of hypoxic rabbit hearts and papillary muscles. The response to blocking of the inward rectifier was studied at three external K+ concentration: 2.5, 5, and 7.5 mM. 2. Hypoxia produced a progressive decline in action potential duration (APD) that levelled off after 15 to 20 min. Steady state APD values at 25% and 95% repolarization (APD25 and APD95) were 26.0 +/- 1.9% and 42.2 +/- 2.4% of controls respectively. 3. Tetraethylammonium (TEA, 10 mM) delayed but did not reduce APD shortening at the steady state. 4. Blocking of IK1 with a mixture of 0.2 mM Ba2+ and 4 mM Cs+ lengthened APD in normoxia and prevented APD95 shortening in hypoxia. The APD25 shortening was significantly attenuated at all [K]o. 5. Glibenclamide (Glib, 30 microM) did not prevent APD shortening, but produced a progressive action potential (AP) lengthening after 15 min of hypoxia. Steady levels of 48 +/- 3.5% and 62 +/- 5.0% of controls for APD25 and APD95 respectively were reached after 45 min. 6. The relation between APD25 and pacing rate was determined in normoxic and hypoxic papillary muscles and the effects of 2 mM 4-aminopyridine (4-AP) were examined. Hypoxia attenuated the APD25 shortening currently observed when the stimulation rate was lowered from 1 to 0.1 Hz without altering the plateau reduction occurring at frequencies above 2 Hz. These effects were potentiated by 4-AP.7. Our data suggest that the accelerated AP repolarization in hypoxic rabbit myocardium represents a delicate balance of several outward currents: IKI, IK-ATP. and at least one yet unidentified current component rather insensitive to changes in [K]o and to K+ channel blockers.
Ruiz Petrich
E
E
Department of Physiology and Biophysics, Faculty of Medicine, University of Sherbrooke, Québec, Canada.
Leblanc
N
N
deLorenzi
F
F
Allard
Y
Y
Schanne
O F
OF
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D001464:Barium / Q000494:pharmacology; D017609:Barium Compounds; D002586:Cesium / Q000494:pharmacology; D002712:Chlorides; D004594:Electrophysiology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D010210:Papillary Muscles / Q000187:drug effects*; D010477:Perfusion; D015221:Potassium Channels / Q000187:drug effects*; D011817:Rabbits; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D017609:Barium Compounds; D002712:Chlorides; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; C024986:barium chloride; D002586:Cesium; D001464:Barium; D019789:Tetraethylammonium; C028019:cesium chloride; D005905:Glyburide