Multiple sulfonylurea-sensitive potassium channels: a novel subtype modulated by dopamine.
In single channel patch-clamp recordings from freshly dissociated rat corpus striatum (caudate-putamen) neurons, the sulfonylurea drugs tolbutamide and glibenclamide caused a concentration-dependent blockade of a K+ channel that is activated by D2 dopamine receptor agonists. Tolbutamide was about 10-100 times more potent than glibenclamide, a rank-order potency opposite to that seen at previously described adenosine triphosphate-sensitive K+ channels. The channel also was poorly activated by diazoxide, which is a known opener of adenosine triphosphate-sensitive K+ channels. However, like adenosine triphosphate-sensitive channels, it opened in the absence of dopaminergic agonist when the cells were treated with the metabolic inhibitor rotenone, indicating that channel openings occur under energy-depleting conditions. This suggests the existence of a novel, pharmacologically distinct class of sulfonyl-urea-sensitive K+ channels, regulated metabolically and also mediating dopaminergic neurotransmission.
Lin
Y J
YJ
Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts 02115.
Greif
G J
GJ
Freedman
J E
JE
D000818:Animals; D004298:Dopamine / Q000502:physiology*; D005905:Glyburide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014044:Tolbutamide / Q000494:pharmacology*
D015221:Potassium Channels; D014044:Tolbutamide; D005905:Glyburide; D004298:Dopamine