CHARACTERIZATION OF THE ADENOSINE A(1) RECEPTOR-ACTIVATED POTASSIUM CURRENT IN RAT LOCUS-CERULEUS NEURONS

The effect of adenosine on locus ceruleus neurons was investigated wit h intracellular recording in a totally submerged brain slice preparati on. Bath application of adenosine (100 mu M) hyperpolarized locus ceru leus neurons and inhibited their spontaneous firing; under voltage-cla mp conditions, adenosine activated an inwardly rectifying, outward cur rent (I-Ado). The reversal potential of the I-Ado was -110 mV and shif ted by 59.2 mV per 10-fold change in external K+ concentration, very c lose to the shift predicted by the Nernst equation for a pure K+ curre nt. The I-Ado was due to a direct postsynaptic action, because it pers isted in low Ca++/high Mg++ media that block Ca++-dependent neurotrans mitter release. The I-Ado was not blocked by glibenclamide, which indi cates that it is not mediated by ATP-dependent K+ channels. The adenos ine-activated current was concentration-dependent (10 mu M-1 mM adenos ine) and was blocked by the selective A(1) antagonist 8-cyclopentylthe ophylline in a competitive manner. Schild analysis in two neurons yiel ded estimates of the K-d value for 8-cyclopentyltheophylline of 1.4 an d 4.6 nM, which indicates that the I-Ado is mediated by A(1) adenosine receptors. The adenosine-induced hyperpolarization, inhibition of fir ing and activation of outward current were blocked by external barium, but not by 4-aminopyridine. By contrast, we have previously shown tha t adenosine enhances A-current, thereby reducing action potential dura tion in locus ceruleus neurons, and these effects are blocked by 4-ami nopyridine but not barium. These data indicate that the adenosine-indu ced hyperpolarization and inhibition of firing are mediated by the I-A do and that these effects are independent of adenosine's enhancement o f A-current.