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

Abstract

1. The aim of the present study was to characterize the pharmacological properties of the adenosine 5'-triphosphate(ATP)-sensitive K+ channel (K(ATP)-channel) on the somata of spiny neurones in rat caudate nucleus and to compare them with those of β-cells. For that purpose we tested the effects of several K(ATP)-channel-inhibiting and -activating drugs on the opening activity of the K(ATP)-channel in caudate nucleus by use of the patch-clamp technique. In addition, the modulation of drug responses by cytosolic nucleotides was examined. 2. When K(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(ATP)-channel activity half-maximally at 0.4 μM, 0.4 μM and about 0.5 nM, respectively. 3. In inside-out patches (presence of 0.7 mM free Mg2+ at the cytoplasmic membrane side), tolbutamide (0.1 mM) caused only partial inhibition of K(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). 4. 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. 5. In the presence of 0.1 mM ATP, diazoxide activated K(ATP)-channels half-maximally at 38 μM. 6. When K(ATP)-channel activity was inhibited by 0.1 mM ATP, (-)-pinacidil (0.5 mM) elicited a slight activation of K(ATP)-channels in caudate nucleus, whereas (+)-pinacidil (0.5 mM) and lemakalim (0.3 mM) were ineffective. 7. Since our data indicate similar control by drugs and nucleotides of K(ATP)-channels in the somata of spiny neurones and pancreatic β-cells, we conclude that the high affinity sulphonylurea receptors of these tissues are probably closely related.