ALPHA(2)-ADRENOCEPTOR-MEDIATED POTASSIUM CURRENTS IN ACUTELY DISSOCIATED RAT LOCUS-COERULEUS NEURONS

1. The noradrenaline (NA)-activated response was investigated in neuro nes acutely dissociated from the rat locus coeruleus (LC) using nystat in-perforated, conventional whole-cell and inside-out patch recording modes under current-and voltage-clamp conditions. 2. Under current-cla mp conditions, NA hyperpolarized the LC neurones, abolishing the spont aneous action potentials. In voltage-clamp studies, NA induced an inwa rdly rectifying K+ current (I-NA) in a concentration-dependent manner with a half-maximum effective concentration of 2.2 x 10(-7) M. 3. I-NA was mimicked by the alpha(2)-agonist UK14304 but was inhibited by eit her the alpha(2A)/alpha(2C) antagonist ARC239 or the alpha(1)- and alp ha(2B)/alpha(2C) antagonist prazosin, suggesting the contribution of a lpha(2B)alpha(2C) adrenoceptors. 4. I-NA was inhibited by the intracel lular application of GDP beta S but fully activated by intracellular p erfusion of GTPyS. 5. In the inside-out recording mode, the applicatio n of GTP to the cytoplasmic side of the patch membrane markedly enhanc ed the open probability of the NA-activated single channels which repr esented the inwardly rectifying properties.6. These results indicate t hat the activation of alpha(2B)/alpha(2C) adrenoceptors coupled with G TP-binding protein directly activates the inwardly rectifying Kf curre nts in rat LC neurones, thus resulting in a decrease in the spontaneou s firing activities.