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 α2-agonist UK14304 but was inhibited by either the α(2B)/α(2C) antagonist ARC239 or the α1- and α(2B)/α(2C) antagonist prazosin, suggesting the contribution of α(2B)/α(2C) adrenoceptors. 4. I(NA) was inhibited by the intracellular application of GDPβS but fully activated by intracellular perfusion of GTPγS. 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 α(2B)/α(2C) adrenoceptors coupled with GTP-binding protein directly activates the inwardly rectifying K+ currents in rat LC neurones, thus resulting in a decrease in the spontaneous firing activities.
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