Facilitation of beta-adrenoceptor-mediated slow channel responses by hypoxia in guinea pig ventricular myocardium.
The effects of hypoxia on the beta-adrenoceptor-mediated slow channel responses of guinea pig ventricular muscle in a potassium-rich (27 mM) solution containing Ba2+ were examined using microelectrode techniques. Isoproterenol produced a small depolarization of the resting membrane and also induced repetitive discharges of action potentials at higher concentrations, mainly due to a beta-adrenoceptor-mediated increase in the slow channel conductance. Two different threshold concentrations of isoproterenol, one for inducing depolarization and one for inducing automatic activity, were measured to assess myocardial responsiveness to catecholamines. During hypoxia, the electrically triggered slow upstroke action potentials of muscle were gradually depressed and catecholamine-induced membrane responses mediated by the beta-adrenoceptor/slow channel system were enhanced. The enhancement of the catecholamine effects was accelerated by acidosis and reversed by reoxygenation. Methyl xanthine-induced responses, similar to those induced by catecholamines, were also enhanced during hypoxia. It is suggested that not only changes of catecholamine-beta-adrenoceptor interaction, but also changes of intracellular metabolic processes, may be responsible, at least in part, for the enhancement of abnormal automatic activity mediated by the myocardial beta-adrenoceptor/slow channel system under hypoxic conditions.
Hasegawa
J
J
Department of Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.
Watanabe
M
M
Matsumoto
T
T
Manabe
I
I
Doi
T
T
Kotake
H
H
Mashiba
H
H
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D002110:Caffeine / Q000494:pharmacology; D002395:Catecholamines / Q000502:physiology; D004594:Electrophysiology; D006168:Guinea Pigs; D006321:Heart / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D002395:Catecholamines; D007473:Ion Channels; D011943:Receptors, Adrenergic, beta; D002110:Caffeine; D007545:Isoproterenol