K sub(ATP)-channel on the somata of spiny neurones in rat caudate nucleus: Regulation by drugs and nucleotides

The aim of the present study was to characterize the pharmacological properties of the adenosine 5'-triphosphate(ATP)-sensitive K super(+) channel (K sub(ATP)-channel) on the somata of spiny neurones in rat caudate nucleus and to compare them with those of beta -cells. For that purpose we tested the effects of several K sub(ATP)-channel-inhibiting and -activating drugs on the opening activity of the K sub(ATP)-channel in caudate nucleus by use of the patch-clamp technique. In addition, the modulation of drug responses by cytosolic nucleotides was examined. When K sub(ATP)-channels in caudate nucleus were activated in cell-attached patches by inhibition of mitochondrial energy production, meglitinide (a benzoic acid derivative), Hoe36320 (a sulphonylurea of low lipophilicity) and glipizide reduced K sub(ATP)-channel activity half-maximally at 0.4 mu M, 0.4 mu M and about 0.5 nM, respectively. In inside-out patches (presence of 0.7 mM free Mg super(2+) at the cytoplasmic membrane side), tolbutamide (0.1 mM) caused only partial inhibition of K sub(ATP)-channels in the absence of cytosolic nucleotides but complete inhibition in the simultaneous presence of the channel-activating nucleotide guanosine 5'-diphosphate (GDP; 1 mM) and the channel-inhibiting nucleotide adenylyl-imidodiphosphate (AMP-PNP; 0.2 mM). Diazoxide (0.3 mM) strongly increased channel activity in the presence of ATP (0.1 mM) or GDP (0.03 mM), but was ineffective in the presence of AMP-PNP (0.1 mM). In the absence of cytosolic nucleotides diazoxide even decreased channel activity. In the presence of 0.1 mM ATP, diazoxide activated K sub(ATP)-channels half-maximally at 38 mu M. When K sub(ATP)-channel activity was inhibited by 0.1 mM ATP, (-)-pinacidil (0.5 mM) elicited a slight activation of K sub(ATP)-channels in caudate nucleus, whereas (+)-pinacidil (0.5 mM) and lemakalim (0.3 mM) were ineffective. Since our data indicate similar control by drugs and nucleotides of K sub(ATP)-channels in the somata of spiny neurones and pancreatic beta -cells, we conclude that the high affinity sulphonylurea receptors of these tissues are probably closely related.