Characterization of the adenosine A1 receptor-activated potassium current in rat locus ceruleus neurons.
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.
Pan
W J
WJ
Department of Physiology and Biophysics, University of Illinois at Chicago, USA.
Osmanović
S S
SS
Shefner
S A
SA
D015761:4-Aminopyridine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D008125:Locus Coeruleus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D015221:Potassium Channels; D018047:Receptors, Purinergic P1; D001464:Barium; C053907:8-cyclopentyl-1,3-dimethylxanthine; D015761:4-Aminopyridine; D013806:Theophylline; D000241:Adenosine; D005905:Glyburide