The high-affinity sulphonylurea receptor regulates KATP channels in nerve terminals of the rat motor cortex.
The coexpression of sulphonylurea binding sites and ATP-sensitive K+(KATP) channels was examined in the rat motor cortex, an area of the CNS exhibiting a high density of sulphonylurea binding. These channels were not detected on neuronal cell bodies, but sulphonylurea-sensitive KATP channels and charybdotoxin-sensitive, large-conductance calcium-activated K+ BKCa channels were detected by patch clamping of fused nerve terminals from the motor cortex. Subcellular fractionation revealed that high-affinity sulphonylurea binding sites were enriched in the nerve terminal fraction, whereas glibenclamide increased calcium-independent glutamate efflux from isolated nerve terminals. It is concluded that neuronal sulphonylurea receptors and KATP channels are functionally linked in the motor cortex and that they are both selectively expressed in nerve terminals, where the KATP channel may serve to limit glutamate release under conditions of metabolic stress.
Lee
K
K
Department of Pharmacology, University of Cambridge, England.
Dixon
A K
AK
Rowe
I C
IC
Ashford
M L
ML
Richardson
P J
PJ
D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D018698:Glutamic Acid / Q000187:drug effects / Q000378:metabolism; D005905:Glyburide / Q000378:metabolism / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000494:pharmacology; D009044:Motor Cortex / Q000166:cytology*; D009411:Nerve Endings / Q000737:chemistry* / Q000187:drug effects; D009474:Neurons / Q000737:chemistry*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000378:metabolism*; D013453:Sulfonylurea Compounds / Q000494:pharmacology; D064233:Sulfonylurea Receptors; D014316:Tritium / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D007004:Hypoglycemic Agents; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D013453:Sulfonylurea Compounds; D064233:Sulfonylurea Receptors; D014316:Tritium; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D005905:Glyburide; D002118:Calcium