Multiple sulfonylurea-sensitive potassium channels: a novel subtype modulated by dopamine

Abstract

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.