Role of alpha-Adrenergic Receptors in the Development of Delayed Afterdepolarization

ABSTRACT

BACKGROUND: To investigate the role of alpha-adrenergic receptors in the development of delayed afterdepolarization, the effect of alpha-adrenoceptor stimulation and blockade on ouabain induced delayed afterdepolarization(DDAD) was examined in rabbit heart Purkinje fibers. METHODS: Purkinje fibers, taken from adult rabbit(1.8 - 2.0kg) heart anesthetized with penobarbital, were mounted in a Luicite chamber and superfused with Tyrode's solution. The transmembrane potentials were measured by the conventional microelectrode technique while the fibers were being stimulated with rectangular pulses of 50% above threshold voltage. The delayed afterdepolarizations were induced by overdrive excitation in the presence of ouabain. RESULTS: Delayed afterdepolarizations were not observed during superfusion of the control Tyrode's solution containing propranolol(5x10(-7)M). However, the addition of ouabain in the presence of propranolol elicited DADs which were dose-, time- and drive cycle length- dependent. Phenylephrine(PE ; 10(-7)M), and alpha-adrenoceptor agonist, potentiated the ouabain-induced DAD during the initial superfusion(for 10 or 20 min) of the test Tyrode's solution. However, it was followed by attenuating-effects after a superfusion time of 50 to 60 min. Both effects showed ouabain dose-dependence. Ouabain(2x10(-7)M), in the presence of propranolol, depolarized the maximum diastolic potential and shortened the action potential duration, and the addition of PE(10(-7)M) did not affect the characteristics of action potential except a decrease in velocity of phase 0 depolarization. Prazosin, an alpha1-adrenoceptor antagonist, inhibited the PE's enhancing effects of ouabaininduced DDAD at 20 min superfusion, but did not affect the attenuating-effects of PE at 60 min superfusion. On the other hand, yohimbine, an alpha2-adrenoceptor antagonist, did not affect the PE's DAD potentiating-effects at 20 min superfusion, but inhibited the attenunating-effects of PE at 60 min superfusion. CONCLUSION: It is inferred that alpha-adrenergic stimulation induce delayed afterdepolarization and triggered activity in the rabbits, being responsible for the arrhythmia development, and the effects are mainly due to the action of alpha1-subtpe adrenoceptor stimulation.