KATP channel activation in a rabbit model of chronic myocardial hypoxia.
Increased tolerance to ischemia exhibited in chronically hypoxia immature rabbit hearts is associated with increased activation of ATP-sensitive potassium (KATP) channels. We determined whether exposure to hypoxia from birth alters the electrophysiological characteristics of Purkinje fibers obtained from rabbits (n = 12/group) which were raised in a normoxic (F O2 = 0.21) or hypoxic (F1O2 = 0.12) environment from birth to 9 days of age and the involvement of the KATP channel. The endocardial surface was exposed and impaled with microelectrodes to record action potential characteristics from Purkinje fibers under control conditions and following exposure to glibenclamide (3 microM). Action potential durations (APD)90 in Purkinje fibers were significantly shorter in hypoxic hearts compared with normoxic controls (110 +/- 5 ms v 121 +/- 4 ms). Glibenclamide increased APD90 in hypoxic hearts (120 +/- 4 ms) to values similar to those observed in normoxic controls (121 +/- 4 ms). Glibenclamide had no effect on APD90 in normoxic hearts. Maximum diastolic potential was more negative in hypoxic hearts and this effect was attenuated by glibenclamide. We conclude that chronic myocardial hypoxia results in a shorter APD as compared with normoxic controls by enhanced activation of KATP channels.
Baker
J E
JE
Department of Pharmacology, Medical College of Wisconsin, Milwaukee 53226, USA.
Contney
S J
SJ
Gross
G J
GJ
Bosnjak
Z J
ZJ
D000200:Action Potentials / Q000187:drug effects; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002908:Chronic Disease; D004594:Electrophysiology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006321:Heart / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D011247:Pregnancy; D011690:Purkinje Fibers / Q000502:physiology; D011817:Rabbits
D007004:Hypoglycemic Agents; D015221:Potassium Channels; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D005905:Glyburide