Im. Stanford et Mg. Lacey, ELECTROPHYSIOLOGICAL INVESTIGATION OF ADENOSINE TRISPHOSPHATE-SENSITIVE POTASSIUM CHANNELS IN THE RAT SUBSTANTIA-NIGRA PARS RETICULATA, Neuroscience, 74(2), 1996, pp. 499-509
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.