Glucose dependent K+-channels in pancreatic?-cells are regulated by intracellular ATP

Rorsman, Patrik; Trube, G.

doi:10.1007/bf00595682

Cited by 386 publications

(260 citation statements)

References 32 publications

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“…nal application of caesium and barium, properties which are The sequence of BIR 1 is almost identical (98%) with GIRK-2 shared with native KAT P channels [6,18,19].…”

Section: Resultsmentioning

confidence: 96%

Cloning and functional expression of the cDNA encoding an inwardly‐rectifying potassium channel expressed in pancreatic β‐cells and in the brain

et al. 1995

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Recently, a KAvp channel has been cloned from cardiac musAbstract A eDNA clone encoding an inwardly-rectifying Kcle [6]. This channel (rCKAvp; KATp-I ) belongs to a family of channel (BIR1) was isolated from insulinoma cells. The predicted inwardly rectifying potassium channels [7,[12][13][14][15][16]. All members amino acid sequence shares 72% identity with the cardiac ATPsensitive K-channel rCKAT e (KaTe-1; [6]). The mRNA is expressed of this family show inward rectification which is at least in part in the brain and insulinoma cells. Heterologous expression in induced by intracellular cations which act as voltage-dependent Xenopus oocytes produced currents which were K+-selective, blocking particles and inhibit outward K+-fluxes [8,17]. The time-independent and showed inward rectification. The currents molecular architecture of the inward rectifier channels is were blocked by external barium and caesium, but insensitive to thought to consist of two transmembrane domains (TMs) with tolbutamide and diazoxide. In inside-out patches, channel activity both N-and C-termini residing within the cell. These TMs are was not blocked by 1 mM internal ATE The sequence homology linked by a highly conserved segment, the P-region, which is with KATe-1 suggests that BIR1 is a subunit of a brain and l~-cell believed to line the channel pore and within which resides the KAT e channel. However, pharmacological differences and the lack K÷-selectivity filter [10,11]; only the P-region shows high hoof ATP-sensitivity, suggest that if, this is the case, heterologous mology with the voltage-gated K ÷ channels. Tissue distribution subunits must exert strong modulatory influences on the native channel, studies showed that KATp-1 mRNA is not expressed in fl-cells [6], suggesting that the fl-cell KAvp channel is a different protein. Key words: K-channel; Inward rectifyer; ATP-sensitive An additional K-ATP channel, uKAT P-1, has also been cloned K-channel; Pancreatic fl-cell; BIR 1 and although widely expressed is not found in insulin-secreting cell lines [13]. We now report the cloning and functional expression of an inwardly-rectifying K-channel with homology to 1. Introduction KAT P-I which is found in fl-cells and brain.The fl-cell ATP-sensitive potassium channel (KAvp channel) plays a central role in glucose-stimulated insulin secretion by 2. Materials and methods linking metabolic and membrane events involved in stimulussecretion coupling [3,5]. At the resting potential of the unstim-2.1. Cloning of BIR1 ulated fl-cell, the KAvp channel is spontaneously active. Glucose Poly(A) ÷ RNA was isolated from RINm5F cells using a Fast Track metabolism produces a concentration-dependent inhibition of RNA isolation kit (Invitrogen), and converted to eDNA by reverse transcription with random primers. Oligonucleotides directed to bases channel activity which is believed to be mediated by associated 471~491 and 632-652 of KATp-1 were employed in the polymerase chain changes in the intracellular concentrations of ATP and ADP.reaction [7] (94°C, 30...

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“…nal application of caesium and barium, properties which are The sequence of BIR 1 is almost identical (98%) with GIRK-2 shared with native KAT P channels [6,18,19].…”

Section: Resultsmentioning

confidence: 96%

Cloning and functional expression of the cDNA encoding an inwardly‐rectifying potassium channel expressed in pancreatic β‐cells and in the brain

et al. 1995

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“…In contrast, adrenaline (100pM) was without effect on 86Rb efflux under the same conditions. In 6mm glucose, most ATP-sensitive K+ channels are closed (Rorsman & Trube, 1985;Misler et al, 1986;Ashcroft et al, 1988) and 86Rb effiux is low and stable. Diazoxide (100pM), an opener of ATP-sensitive K+ channels in fl-cells (Trube et al, 1986), caused a marked acceleration of 86Rb effiux.…”

Section: Resultsmentioning

confidence: 99%

“…Diazoxide (100pM), an opener of ATP-sensitive K+ channels in fl-cells (Trube et al, 1986), caused a marked acceleration of 86Rb effiux. Clonidine Effects of clonidine and adrenaline on A TP-sensitive K + currents At physiological ATP concentrations, the whole cell ATPsensitive K+ current is small because most of the channels are inhibited (Rorsman & Trube, 1985). When the cell is dialysed with a pipette solution containing a lower than physiological ATP concentration, ATP-sensitive K+ currents activate with time following the establishment of the whole cell configuration and then decline at a rate dependent on the ATP concentration (Trube et al, 1986;Garrino et al, 1989).…”

Section: Resultsmentioning

confidence: 99%

Clonidine inhibits ATP‐sensitive K⁺channels in mouse pancreatic β‐cells

Plant

Jonas²,

Henquin

1991

British J Pharmacology

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1 The effects of clonidine and adrenaline on adenosine 5'-triphosphate (ATP)-sensitive K + channels were studied in pancreatic #-cells from normal mice.2 When perifused with a medium containing 1 mm glucose, many of the ATP-sensitive K+ channels in the fl-cell membrane are open. Under these conditions, clonidine (5-100,uM) reversibly decreased 86Rb efflux from the islets, whereas adrenaline was ineffective at concentrations up to 100,UM.3 In 6 mm glucose, most of the ATP-sensitive K + channels in the fl-cell membrane are closed. Opening these channels by diazoxide (100pM) caused a marked acceleration of 86Rb efflux from the islets, which was attenuated by 100pM clonidine.4 ATP-sensitive K+ currents were measured in single fl-cells by the whole cell mode of the patch-clamp technique. At concentrations above 4pM, clonidine reversibly inhibited the ATP-sensitive K+ current in a dose-dependent manner.5 Voltage-sensitive K+ currents were unaffected by 20OpM but decreased slightly by 100pM clonidine.6 Calcium currents, measured by the whole cell or perforated patch technique, were unaffected by clonidine at concentrations up to 100pM. 7 It is concluded that high concentrations of the a2-adrenoceptor agonist clonidine, but not of adrenaline, can inhibit ATP-sensitive K+ channels in pancreatic fl-cells. Other ionic channels are only slightly affected or unaffected.

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“…Glucose is thought to stimulate insulin release by a similar mechanism (Atwater et al, 1978;Ashcroft et al, 1984). The glucose-sensitive pancreatic K+ channel and the K+ channel blocked by glibenclamide, a more potent sulphonylurea than tolbutamide, have both been shown to be regulated by intracellular ATP (Cook & Hales, 1984;Rorsman & Trube, 1985;Schmid-Antomarchi et al, 1987). These results suggest that glucose and the sulphonylureas may act on the same membrane K + channel in pancreatic islet cells.…”

Section: Introductionmentioning

confidence: 93%

Inhibition by glibenclamide of the vasorelaxant action of cromakalim in the rat

Buckingham

Hamilton

Howlett

et al. 1989

British J Pharmacology

117

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In rat isolated thoracic aortic rings pre‐contracted with noradrenaline (10−6 m), cromakalim (3 × 10−7‐3 × 10−5 m) produced concentration‐related relaxation. This effect was progressively inhibited by increasing concentrations of the anti‐diabetic sulphonylurea drug, glibenclamide (10−6‐10−5 m). In rat isolated portal veins, cromakalim (3 × 10−8‐10−6 m) produced concentration‐related inhibition of the spontaneous contractive activity and glibenclamide (3 × 10−7‐3 × 10−6 m) prevented this inhibitory action in a concentration‐dependent manner. In both rat aortic rings and portal veins, cromakalim (10−5 m) stimulated 86Rb efflux. Prior exposure to glibenclamide (10−7‐10−6 m) produced a concentration‐related inhibition of this response. In conscious rats, cromakalim, 0.075 mg kg−1 i.v., produced a rapid and sustained fall in arterial blood pressure which was not influenced by pretreatment (2 h) with a large oral dose of glibenclamide (100 mg kg−1). In conscious rats, the hypotensive action of cromakalim, 0.075 mg kg−1 i.v., was abolished by pretreatment (30 min) with glibenclamide, 20 mg kg−1, given by the intravenous route. The results suggest that the vasorelaxant and hypotensive actions of cromakalim involve a K+ channel which can be inhibited by glibenclamide, but which may be distinct from the ATP‐sensitive K+ channel of the pancreatic β‐cell.

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Glucose dependent K+-channels in pancreatic?-cells are regulated by intracellular ATP

Cited by 386 publications

References 32 publications

Cloning and functional expression of the cDNA encoding an inwardly‐rectifying potassium channel expressed in pancreatic β‐cells and in the brain

Cloning and functional expression of the cDNA encoding an inwardly‐rectifying potassium channel expressed in pancreatic β‐cells and in the brain

Clonidine inhibits ATP‐sensitive K⁺channels in mouse pancreatic β‐cells

Inhibition by glibenclamide of the vasorelaxant action of cromakalim in the rat

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Glucose dependent K+-channels in pancreatic?-cells are regulated by intracellular ATP

Cited by 386 publications

References 32 publications

Cloning and functional expression of the cDNA encoding an inwardly‐rectifying potassium channel expressed in pancreatic β‐cells and in the brain

Cloning and functional expression of the cDNA encoding an inwardly‐rectifying potassium channel expressed in pancreatic β‐cells and in the brain

Clonidine inhibits ATP‐sensitive K+channels in mouse pancreatic β‐cells

Inhibition by glibenclamide of the vasorelaxant action of cromakalim in the rat

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Clonidine inhibits ATP‐sensitive K⁺channels in mouse pancreatic β‐cells