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 tolb utamide and glibenclamide caused a concentration-dependent blockade of a K+ channel that is activated by D2 dopamine receptor agonists. Tolb utamide 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 activa ted by diazoxide, which is a known opener of adenosine triphosphate-se nsitive K+ channels. However, like adenosine triphosphate-sensitive ch annels, it opened in the absence of dopaminergic agonist when the cell s were treated with the metabolic inhibitor rotenone, indicating that channel openings occur under energy-depleting conditions. This suggest s the existence of a novel, pharmacologically distinct class of sulfon ylurea-sensitive K+ channels, regulated metabolically and also mediati ng dopaminergic neurotransmission.