Putative pre- and postsynaptic ATP-sensitive potassium channels in the rat substantia nigra in vitro.
Pre- and postsynaptic adenosine 5'-triphosphate-sensitive potassium (ATP-K+) currents were studied using whole-cell recordings from substantia nigra zona compacta "principal" neurons in midbrain slices. The GABAA and GABAB receptor-mediated synaptic potentials were unaffected by the ATP-K+ channel inhibitor glibenclamide (30 microM) or by the opener diazoxide (500 microM), indicating that ATP-K+ channels on GABA-ergic terminals are not active, nor can they be activated pharmacologically, under control conditions. However, application of a glucose-free solution to reduce intracellular ATP levels caused a reduction of the GABAB IPSP in all neurons. This was substantially reversed by the sulfonylurea inhibitor tolbutamide (300 microM) in 50% of the neurons tested. The reduction of the GABAB IPSP was a presynaptic effect since postsynaptic hyperpolarizations induced by the GABAB receptor agonist baclofen (10 microM) were unaffected by glucose-free solutions. Diazoxide (500 microM) induced a slowly developing hyperpolarization or outward current in 64% of principal neurons, which was tolbutamide- (100-300 microM) or glibenclamide- (30 microM) sensitive. In contrast, the GABAB receptor agonist baclofen (30 microM) induced a rapid hyperpolarization or outward current in all neurons tested that was unaffected by tolbutamide (300 microM). Although both the diazoxide-induced current and the baclofen-induced current were inhibited by Ba2+ (300 microM), the currents elicited by diazoxide and baclofen summated. The reversal potential for the diazoxide-induced current was also less negative than that for baclofen, which was close to EK. 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 addition to activating a potassium current. Our results suggest that functional ATP-K+ channels exist both pre- and postsynaptically in the SN, where they modulate the activity of principal neurons. They are different to the potassium channels activated by the GABAB receptor agonist baclofen.
Watts
A E
AE
Pharmacology Department, School of Medical Sciences, University of Bristol, UK.
Hicks
G A
GA
Henderson
G
G
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D017609:Barium Compounds / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010721:Phosphinic Acids / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology*; D013378:Substantia Nigra / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014044:Tolbutamide / Q000494:pharmacology
D017609:Barium Compounds; D002712:Chlorides; D058787:GABA-A Receptor Antagonists; D010721:Phosphinic Acids; D015221:Potassium Channels; D011412:Propanolamines; D011963:Receptors, GABA-A; C024986:barium chloride; C085075:CGP 55845A; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D014044:Tolbutamide; D001418:Baclofen; D005947:Glucose; D003981:Diazoxide; D001640:Bicuculline