Ae. Watts et al., PUTATIVE PRESYNAPTIC AND POSTSYNAPTIC ATP-SENSITIVE POTASSIUM CHANNELS IN THE RAT SUBSTANTIA-NIGRA IN-VITRO, The Journal of neuroscience, 15(4), 1995, pp. 3065-3074
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.