Locus coeruleus activity in vitro: intrinsic regulation by a calcium-dependent potassium conductance but not alpha 2-adrenoceptors.

Locus coeruleus neurons recorded intracellularly in rat brainstem slices exhibited spontaneous activity and a marked afterhyperpolarization following a burst of spikes. This afterhyperpolarization was associated with an increase in membrane conductance and resulted in a marked postactivation inhibition of spontaneous activity. Since the reversal potential of the afterhyperpolarization was found to be virtually identical when recorded with KCl or potassium acetate-filled electrodes and shifted in the hyperpolarizing and depolarizing direction with decreases and increases in extracellular potassium concentrations, respectively, the afterhyperpolarization seen following a burst of spikes in this cell group appears to be mediated by an increase in potassium conductance. The afterhyperpolarization and postactivation inhibition were markedly attenuated by reducing calcium influx by either omitting extracellular calcium in the bathing medium or blocking calcium channels with manganese or cadmium. Thus, the afterhyperpolarization and the resulting postactivation inhibition appear to be largely mediated by the activation of a calcium-dependent potassium conductance. Previous reports in vivo have suggested that activation of alpha 2-adrenoceptors by norepinephrine release from recurrent axons or dendrites may mediate self-inhibition in the locus coeruleus. In this study, we examined the effect of blocking alpha 2-adrenoceptors on the afterhyperpolarization and postactivation inhibition. Administration of the alpha 2-adrenoceptor antagonist piperoxane failed to produce any changes in either of these parameters, suggesting that at least in vitro the afterhyperpolarization and postactivation inhibition seen in locus coeruleus neurons do not result from the activation of alpha 2-adrenoceptors.