Abstract
The effect of adenosine on locus ceruleus neurons was investigated with intracellular recording in a totally submerged brain slice preparation. Bath application of adenosine (100 microM) hyperpolarized locus ceruleus neurons and inhibited their spontaneous firing; under voltage-clamp conditions, adenosine activated an inwardly rectifying, outward current (IAdo). The reversal potential of the IAdo was -110 mV and shifted by 59.2 mV per 10-fold change in external K+ concentration, very close to the shift predicted by the Nernst equation for a pure K+ current. The IAdo was due to a direct postsynaptic action, because it persisted in low Ca++/high Mg++ media that block Ca(++)-dependent neurotransmitter release. The IAdo was not blocked by glibenclamide, which indicates that it is not mediated by ATP-dependent K+ channels. The adenosine-activated current was concentration-dependent (10 microM-1 mM adenosine) and was blocked by the selective A1 antagonist 8-cyclopentyltheophylline in a competitive manner. Schild analysis in two neurons yielded estimates of the Kd value for 8-cyclopentyltheophylline of 1.4 and 4.6 nM, which indicates that the IAdo is mediated by A1 adenosine receptors. The adenosine-induced hyperpolarization, inhibition of firing and activation of outward current were blocked by external barium, but not by 4-aminopyridine. By contrast, we have previously shown that adenosine enhances A-current, thereby reducing action potential duration in locus ceruleus neurons, and these effects are blocked by 4-aminopyridine but not barium. These data indicate that the adenosine-induced hyperpolarization and inhibition of firing are mediated by the IAdo and that these effects are independent of adenosine's enhancement of A-current.
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