Effects of GABAergic Agonists on the Action Potential Characteristics in Rat Atria.

Kim, Jae Ha; Yum, Si Chang; Lim, Young Chai

Abstract

The role of gamma aminobutyric acid (GABA) as a central nervous system neurotransmitter has been widely accepted for many years, and therefore, the cardiovascular effects of intravenous GABAergic agonist have been considered as secondary actions of the agent through the vasomotor center in the brain. Recent studies, however, have shown that GABA plays a role in peripheral cardiovascular system directly. Despite ample evidences, the presence of GABAergic receptors in heart is still controversial. The aim of the present study was to clarify the presence of GABAergic receptors in rat atrium by measuring the effects of GABAergic agonist and antagonist on action potential characteristics in vitro, and to examine the interactions of GABAergic agonist and benzodiazepine, which is already established in the CNS, in rat atrial preparations. Both isoguvacine (10(-4), GABAergic agonist, and diazepam (10(-4) M), benzodiazepinergic drug, decreased the maximum rate of phase 0 depolarization (dV/dt(max)), and prolonged the duration of action potential (APD(90)). The other variables of action potentials were not affected by the agents. The decreasing effects of dV/dt(max) by superfusion with the two agents together were greater than those by superfusion with each agent alone. However, the increasing effects of APD(90) were not augmented by superfusion dV/dt(max) -decreasing effects but did not affect the APD(90) incerasing effects of the two agents.These results indicate that GABAergic receptors exist in rat atria and that the dV/dt(max) -decreasing effects of isoguvacine and diazepam are dependent on the GABAergic receptors but APD(90)-increasing effect is not.