PUTATIVE PRESYNAPTIC AND POSTSYNAPTIC ATP-SENSITIVE POTASSIUM CHANNELS IN THE RAT SUBSTANTIA-NIGRA IN-VITRO

Pre- and postsynaptic adenosine 5'-triphosphate-sensitive potassium (A TP-K+) currents were studied using whole-cell recordings from substant ia nigra zona compacta ''principal'' neurons in midbrain slices, The G ABA(A) and GABA(B) receptor-mediated synaptic potentials were unaffect ed by the ATP-K+ channel inhibitor glibenclamide (30 mu M) or by the o pener diazoxide (500 mu M), indicating that ATP-K+ channels on GABA-er gic terminals are not active, nor can they be activated pharmacologica lly, under control conditions, However, application of a glucose-free solution to reduce intracellular ATP levels caused a reduction of the GABA(B) IPSP in all neurons, This was substantially reversed by the su lfonylurea inhibitor tolbutamide (300 mu M) in 50% of the neurons test ed, The reduction of the GABA(B) IPSP was a presynaptic effect since p ostsynaptic hyperpolarizations induced by the GABA(B) receptor agonist baclofen (10 mu M) were unaffected by glucose-free solutions, Diazoxi de (500 mu M) induced a slowly developing hyperpolarization or outward current in 64% of principal neurons, which was tolbutamide- (100-300 mu M) or glibenclamide- (30 mu M) sensitive, In contrast, the GABA(B) receptor agonist baclofen (30 mu M) induced a rapid hyperpolarization or outward current in all neurons tested that was unaffected by tolbut amide (300 mu M). Although both the diazoxide-induced current and the baclofen-induced current were inhibited by Ba2+ (300 mu M), the curren ts elicited by diazoxide and baclofen summated, The reversal potential for the diazoxide-induced current was also less negative than that fo r baclofen, which was close to E(K). In the presence of intracellular cesium, diazoxide induced a tolbutamide-sensitive inward current in a proportion of neurons, indicating that it has other actions in additio n to activating a potassium current, Our results suggest that function al ATP-K+ channels exist both pre- and postsynaptically in the SN, whe re they modulate the activity of principal neurons, They are different to the potassium channels activated by the GABA(B) receptor agonist b aclofen.