Modulation of GABAA receptor-activated current by norepinephrine in cerebellar Purkinje cells.
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.
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D007150:Immunohistochemistry; D007473:Ion Channels / Q000187:drug effects*; D008566:Membranes / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D011689:Purkinje Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*
D007473:Ion Channels; D011943:Receptors, Adrenergic, beta; D011963:Receptors, GABA-A; D000242:Cyclic AMP; D009638:Norepinephrine