Adenosine-induced Mature Cells Of Rat Substantia Gelatinosa Postsynaptic Response

Objective:The present study examined a current response induced by adenosine in substantia gelatinosa (SG) neurons of adult rat spinal cord slices by using the whole-cell patch-clamp technique. Methods:Male adult Sprague-Dawley rats (7-8 weeks old) were anesthetized with urethane (1.2g/kg, intraperitoneal), and then lumol/Lol/Lbosacral laminectomy was performed. The lumbosacral spinal cord (L1-S3) was removed and mounted on a vibrating microslicer and then a 500μmol/L thick transverse slice was cut. The slice was placed on nylon mesh in the recording chamber for electrophysiological recordings. Adenosine and other drugs were applied by superfusion with a change in solutions in the recording chamber. Drugs reached the recording chamber within 20s of switching and a complete exchange of solutions in the slice chamber took less than 30s.Results:In 98 (78 %) out of 125 neurons examined, superfusing adenosine (1mmol/L) induced an outward current at -70 mV; this had a peak amplitude of 18.8 + 1.1 pA (n = 98). This action was dose-dependent in a concentration range of 50-2000 μmol/L with an EC50 value of 177umol/L The adenosine current was enhanced in duration by the nucleoside-transporter inhibitors, NBTI and NBTG. Except for NBTI (5μmol/L), the inhibitors increased the amplitude of the outward currents. The adenosine current reversed its polarity at a potential which was close to the equilibrium potential for K+ and exhibited a linear current-voltage relationship in a range of -150 - -40 mV (n = 5). The adenosine current was suppressed in amplitude by Ba2+ (100μmol/L) and 4-aminopyridine [4-AP, 5mmol/ L; to 42 + 6 % (n = 8) and 56 + 7 % (n = 7), respectively, of control] but not by 4-AP ( 1mmol/L) or tetraethylammonium (5mmol/L; n = 4). The adenosine current was mimicked by an A1 adenosine-receptor agonist, CPA (1μmol/L; 20.7 + 2.8 pA, n = 5; at -70 mV). When examined in a neuron exhibiting the adenosine response, this amplitude was fully depressed in the presence of an A1 adenosine-receptor antagonist, DPCPX (1μmol/L). Conclusion:Known to serve as an important neuromodulator in the central nervous system, adenosine induced an outward current (hyperpolarization) in SG neurons by increasing a potassium conductance through the activation of postsynaptic A1 receptors, resulting in depressing an excitability of the neurons. So adenosine and adenosine A1 receptor agonists have a therapeutic usefulness in neuroprotection.