α2-adrenoceptor-mediated potassium currents in acutely dissociated rat locus coeruleus neurones

1. The noradrenaline (NA)-activated response was investigated in neurones acutely dissociated from the rat locus coeruleus (LC) using nystatin-perforated, conventional whole-cell and inside-out patch recording modes under current-and voltage-clamp conditions. 2. Under current-clamp conditions, NA hyperpolarized the LC neurones, abolishing the spontaneous action potentials. In voltage-clamp studies, NA induced an inwardly 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 either the alpha(2A)/alpha(2C) antagonist ARC239 or the alpha(1)- and alpha(2B)/alpha(2C) antagonist prazosin, suggesting the contribution of alpha(2B)alpha(2C) adrenoceptors. 4. I-NA was inhibited by the intracellular application of GDP beta S but fully activated by intracellular perfusion of GTPyS. 5. In the inside-out recording mode, the application of GTP to the cytoplasmic side of the patch membrane markedly enhanced the open probability of the NA-activated single channels which represented the inwardly rectifying properties. 6. These results indicate that the activation of alpha(2B)/alpha(2C) adrenoceptors coupled with GTP-binding protein directly activates the inwardly rectifying Kf currents in rat LC neurones, thus resulting in a decrease in the spontaneous firing activities.