ELECTROPHYSIOLOGICAL INVESTIGATION OF ADENOSINE TRISPHOSPHATE-SENSITIVE POTASSIUM CHANNELS IN THE RAT SUBSTANTIA-NIGRA PARS RETICULATA

Adenosine trisphosphate-sensitive potassium (K-ATP) channels in the su bstantia nigra pars reticulata were studied in rat brain slices using whole-cell patch clamp recording. Substantia nigra pars reticulata neu rons were identified as such by their spontaneous action potential fir ing at mean rate of 15.3 Hz, virtual absence of hyperpolarization-acti vated inward current I-h, and unresponsiveness to dopamine (30 mu M), quinpirole (10 mu M) and (Met)enkephalin (10 mu M). Intracellular dial ysis with Mg2+-ATP-free pipette solutions caused a slowly developing m embrane hyperpolarization (13 +/- 4 mV), accompanied by a cessation of action potential firing, or an outward current (79 +/- 30 pA at aroun d -60 mV), which were reversed by the sulphonylurea K-ATP channel bloc kers tolbutamide (100 mu M) and glibenclamide (3 mu M). When Mg2+-ATP (2 mM) was included in the recording pipette no membrane hyperpolariza tion or outward current was observed. Neither the sulphonylureas nor t he potassium channel activator lemakalim (200 mu M) altered membrane p otential, firing rate or holding current under these recording conditi ons. The outward current induced by dialysis with Mg2+-ATP-free soluti ons reversed polarity negative to -94 +/- 9 mV (9 cells), close to the estimated K+ equilibrium potential (-105 mV) for the conditions used, and was associated with a conductance increase that was blocked by Ba 2+ (100 mu M). The current blocked by the sulphonylureas had a similar reversal potential (-97 +/- 7 mV; 13 cells), and both currents were v oltage independent over the range -50 to -100 mV with slope conductanc e of approximately 2.0 nS. Outward synaptic currents were evoked by si ngle shock electrical stimulation, in the presence of glutamate recept or antagonists, at a holding potential of -50 mV. These synaptic curre nts were blocked by bicuculline (10 mu M) and reversed polarity at aro und -65 mV, close to the Cl- equilibrium potential, and were thus medi ated by GABA(A) receptors. They were reversibly depressed by 37 +/- 14 % in lemakalim (200 mu M) in 6/12 cells tested, an effect that was par tially reversed by tolbutamide (200 mu M). It is concluded that functi onal K-ATP channels are present both presynaptically and postsynaptica lly in the substantia nigra pars reticulata. Postsynaptic K-ATP channe ls may control excitability in conditions where intracellular ATP is r educed, whereas presynaptic K-ATP channels, sensitive to the potassium channel activator lemakalim, can modulate the release of GABA, which probably arises from fibres of extranigral origin. Pharmacological dif ferences between these two sites could be exploited to treat epilepsie s, dyskinesias and akinesia. Copyright (C) 1996 IBRO. Published by Els evier Science Ltd.