Article date: 1992/12/1
PubMed ID: 1283212
Journal name: Neuroscience (ISSN: 0306-4522)
Previous studies employing extracellular single-unit recording in the intact cerebellum have demonstrated that norepinephrine can potentiate GABA-induced suppression of Purkinje cell spike activity. However, many issues related to the nature of this modulatory phenomenon remain to be resolved. Using whole-cell patch clamp recording, the present study investigated the effect of norepinephrine on GABA-activated membrane currents (IGABA) in solitary Purkinje cells isolated from neonatal rat cerebella following acute dissociation. Exposure of Purkinje cells to norepinephrine at a concentration which, by itself, had no obvious effect on Purkinje cell membrane conductance, consistently augmented IGABA. The catecholamine also potentiated GABA-gated chloride currents as well as muscimol-induced currents in Purkinje cells. Thus, the facilitating effect of norepinephrine on IGABA was attributed to an interaction between norepinephrine and the GABAA receptor-mediated chloride conductance. The effect of norepinephrine could be mimicked by isoproterenol as well as by 8-bromo cAMP, suggesting that a beta-receptor-mediated, cAMP-dependent cascade may underlie the observed heteroreceptor interaction. Our results establish the existence of a postsynaptic mechanism by which norepinephrine, through activation of the beta-adrenoceptor, may modulate GABAA receptor function in cerebellar Purkinje cells. This study provides the groundwork for a detailed investigation into the cascade of membrane and intracellular events underlying such a synergistic modulatory interaction at the cellular and subcellular levels.
Author List: Cheun J E, Yeh H H
Publication Types: Journal Article; Research Support, U.S. Gov't, P.H.S.
Substances mentioned in the article: Ion Channels; Receptors, Adrenergic, beta; Receptors, GABA-A; Cyclic AMP; Norepinephrine;
Mesh terms: Animals; Animals, Newborn/metabolism; Cyclic AMP/metabolism; Immunohistochemistry; Ion Channels/drug effects; Membranes/metabolism; Norepinephrine/pharmacology; Purkinje Cells/drug effects; Rats; Receptors, Adrenergic, beta/physiology; Receptors, GABA-A/drug effects;