Regulation equilibrative nucleoside transporter of adenosine outward currents in adult rat spinal dorsal horn neurons

A current response induced by superfusing adenosine was examined in substantia gelatinosa (SG) neurons of adult rat spinal cord slices by using the whole-cell patch-clamp technique. In 78% of the neurons examined, adenosine induced an outward current at -70 mV [18.8 +/- 1.1 pA (n = 98) at 1 mM] in a dose-dependent manner (EC50 = 177 muM). A similar current was induced by A(1) agonist N-6-cyclopentyladenosine (1 muM), whereas A(1) antagonist 8-cyclopentyl-1,3-dipropylxanthine (1 muM) reversed the adenosine action. The adenosine current reversed its polarity at a potential being close to the equilibrium potential for K+, and was attenuated by Ba2+ (100 muM) and 4-aminopyridine (5 mM) but not tetraethylammonium (5 mM). The adenosine current was enhanced in duration by equilibrative nucleoside-transport (rENT 1) inhibitor S-(4-nitrobenzyl)-6-thioinosine (1 muM) and adenosine deaminase (ADA) inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (1 muM), and slowed in falling phase by adenosine kinase (AK) inhibitor iodotubercidine (1 muM). We conclude that a Ba2+- and 4-aminopyridine-sensitive K+ channel in SG neurons is opened via the activation of A, receptors by adenosine whose level is possibly regulated by rENT1, adenosine deaminase and adenosine kinase. Considering that intrathecally-administered adenosine analogues produce antinociception, the regulatory systems of adenosine may serve as targets for antinociceptive drugs. (C) 2004 Elsevier Inc. All rights reserved.