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Effects of K + channel blockers on the action potential of hypoxic rabbit myocardium
Author(s) -
Petrich Elena Ruiz,
Leblanc Normand,
Lorenzi Fabien,
Allard Yvon,
Schanne Otto F.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14436.x
Subject(s) - glibenclamide , repolarization , hypoxia (environmental) , tetraethylammonium , chemistry , medicine , endocrinology , potassium channel blocker , membrane potential , stimulation , depolarization , channel blocker , 4 aminopyridine , electrophysiology , fissipedia , potassium channel , potassium , oxygen , calcium , biochemistry , organic chemistry , diabetes mellitus
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 + ‐channels 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 + concentrations: 2.5, 5, and 7.5 m m . 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 (APD 25 and APD 95 ) were 26.0 ± 1.9% and 42.2 ± 2.4% of controls respectively. 3 Tetraethylammonium (TEA, 10 m m ) delayed but did not reduce APD shortening at the steady state. 4 Blocking of I K1 with a mixture of 0.2 m m Ba 2+ and 4 m m Cs + lengthened APD in normoxia and prevented APD 95 shortening in hypoxia. The APD 25 shortening was significantly attenuated at all [K] o . 5 Glibenclamide (Glib, 30 μ m ) 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 APD 25 and APD 95 respectively were reached after 45 min. 6 The relation between APD 25 and pacing rate was determined in normoxic and hypoxic papillary muscles and the effects of 2 m m 4‐aminopyridine (4‐AP) were examined. Hypoxia attenuated the APD 25 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: I K1 , I K‐ATP , and at least one yet unidentified current component rather insensitive to changes in [K] o and to K + channel blockers.