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Diabetologia
Published in: Diabetologia 8/2003

01-08-2003 | Review

Voltage-dependent K+ channels in pancreatic beta cells: Role, regulation and potential as therapeutic targets

Authors: Dr. P. E. MacDonald, M. B. Wheeler

Published in: Diabetologia | Issue 8/2003

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Abstract

Insulin secretion from pancreatic islet beta cells is acutely regulated by a complex interplay of metabolic and electrogenic events. The electrogenic mechanism regulating insulin secretion from beta cells is commonly referred to as the ATP-sensitive K+ (KATP) channel dependent pathway. Briefly, an increase in ATP and, perhaps more importantly, a decrease in ADP stimulated by glucose metabolism depolarises the beta cell by closing KATP channels. Membrane depolarisation results in the opening of voltage-dependent Ca2+ channels, and influx of Ca2+ is the main trigger for insulin secretion. Repolarisation of pancreatic beta cell action potential is mediated by the activation of voltage-dependent K+ (Kv) channels. Various Kv channel homologues have been detected in insulin secreting cells, and recent studies have shown a role for specific Kv channels as modulators of insulin secretion. Here we review the evidence supporting a role for Kv channels in the regulation of insulin secretion and discuss the potential and the limitations for beta-cell Kv channels as therapeutic targets. Furthermore, we review recent investigations of mechanisms regulating Kv channels in beta cells, which suggest that Kv channels are active participants in the regulation of beta-cell electrical activity and insulin secretion.
Literature
1.
Aizawa T, Sato Y, Komatsu M (2002) Importance of nonionic signals for glucose-induced biphasic insulin secretion. Diabetes 51 [Suppl 1]:S96–S98
2.
Prentki M, Tornheim K, Corkey BE (1997) Signal transduction mechanisms in nutrient-induced insulin secretion. Diabetologia 40 [Suppl 2]:S32–S41
3.
MacDonald PE, Sewing S, Wang J et al. (2002) Inhibition of Kv2.1 voltage-dependent K+ channels in pancreatic β-cells enhances glucose-dependent insulin secretion. J Biol Chem 277:44938–44945CrossRefPubMed
4.
Henquin JC, Meissner HP, Preissler M (1979) 9-Aminoacridine- and tetraethylammonium-induced reduction of the potassium permeability in pancreatic β-cells. Effects on insulin release and electrical properties. Biochim Biophys Acta 587:579–592CrossRefPubMed
5.
Herchuelz A, Thonnart N, Carpinelli A, Sener A, Malaisse WJ (1980) Regulation of calcium fluxes in rat pancreatic islets: the role of K+ conductance. J Pharmacol Exp Ther 215:213–220PubMed
6.
Komatsu M, Schermerhorn T, Aizawa T, Sharp GW (1995) Glucose stimulation of insulin release in the absence of extracellular Ca2+ and in the absence of any increase in intracellular Ca2+ in rat pancreatic islets. Proc Natl Acad Sci USA 92:10728–10732PubMed
7.
Henquin JC (2000) Triggering and amplifying pathways of regulation of insulin secretion by glucose. Diabetes 49:1751–1760PubMed
8.
Dean PM, Matthews EK (1968) Electrical activity in pancreatic islet cells. Nature 219:389–390PubMed
9.
Henquin JC (1978) D-glucose inhibits potassium efflux from pancreatic islet cells. Nature 271:271–273PubMed
10.
Sehlin J, Taljedal IB (1975) Glucose-induced decrease in Rb+ permeability in pancreatic β-cells. Nature 253:635–636PubMed
11.
Ashcroft FM, Harrison DE, Ashcroft SJ (1984) Glucose induces closure of single potassium channels in isolated rat pancreatic β-cells. Nature 312:446–448PubMed
12.
Cook DL, Hales CN (1984) Intracellular ATP directly blocks K+ channels in pancreatic β-cells. Nature 311:271–273PubMed
13.
Rorsman P, Trube G (1985) Glucose dependent K+-channels in pancreatic β-cells are regulated by intracellular ATP. Pflugers Arch 405:305–309PubMed
14.
Arkhammar P, Nilsson T, Rorsman P, Berggren PO (1987) Inhibition of ATP-regulated K+ channels precedes depolarization-induced increase in cytoplasmic free Ca2+ concentration in pancreatic β-cells. J Biol Chem 262:5448–5454PubMed
15.
Inagaki N, Gonoi T, Clement JP et al. (1995) Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor. Science 270:1166–1170PubMed
16.
Sakura H, Ammala C, Smith PA, Gribble FM, Ashcroft FM (1995) Cloning and functional expression of the cDNA encoding a novel ATP- sensitive potassium channel subunit expressed in pancreatic β-cells, brain, heart and skeletal muscle. FEBS Lett 377:338–344PubMed
17.
Aguilar-Bryan L, Nichols CG, Wechsler SW et al. (1995) Cloning of the β-cell high-affinity sulfonylurea receptor: a regulator of insulin secretion. Science 268:423–426PubMed
18.
Sturgess NC, Ashford ML, Cook DL, Hales CN (1985) The sulphonylurea receptor may be an ATP-sensitive potassium channel. Lancet 2:474–475PubMed
19.
20.
Trube G, Rorsman P, Ohno-Shosaku T (1986) Opposite effects of tolbutamide and diazoxide on the ATP-dependent K+ channel in mouse pancreatic β-cells. Pflugers Arch 407:493–499PubMed
21.
Yabo R, Viktora J, Staquet M, Wolff F (1965) Studies concerning the hyperglycemic effects of diazoxide and its mode of action. Diabetes 14:591–594PubMed
22.
Stabile BE (1997) Islet cell tumors. Gastroenterologist 5:213–232PubMed
23.
Shirland L (2001) When it is more than transient neonatal hypoglycemia: hyperinsulinemia—a case study challenge. Neonatal Netw 20:5–11
24.
Taylor AE (2000) Insulin-lowering medications in polycystic ovary syndrome. Obstet Gynecol Clin North Am 27:583–595PubMed
25.
Meissner HP, Schmelz H (1974) Membrane potential of β-cells in pancreatic islets. Pflugers Arch 351:195–206PubMed
26.
Dean PM, Matthews EK (1970) Electrical activity in pancreatic islet cells: effect of ions. J Physiol 210:265–275PubMed
27.
Atwater I, Dawson CM, Eddlestone GT, Rojas E (1981) Voltage noise measurements across the pancreatic β-cell membrane: calcium channel characteristics. J Physiol 314:195–212PubMed
28.
Rorsman P, Trube G (1986) Calcium and delayed potassium currents in mouse pancreatic β-cells under voltage-clamp conditions. J Physiol (Lond) 374:531–550
29.
Kelly RP, Sutton R, Ashcroft FM (1991) Voltage-activated calcium and potassium currents in human pancreatic β-cells. J Physiol (Lond) 443:175–192
30.
Perez-Reyes E, Wei XY, Castellano A, Birnbaumer L (1990) Molecular diversity of L-type calcium channels. Evidence for alternative splicing of the transcripts of three non-allelic genes. J Biol Chem 265:20430–20436PubMed
31.
Yaney GC, Wheeler MB, Wei X et al. (1992) Cloning of a novel α1-subunit of the voltage-dependent calcium channel from the β-cell. Mol Endocrinol 6:2143–2152PubMed
32.
Seino S, Chen L, Seino M (1992) Cloning of the α1 subunit of a voltage-dependent calcium channel expressed in pancreatic β-cells. Proc Natl Acad Sci USA 89:584–588PubMed
33.
Satin LS (2000) Localized calcium influx in pancreatic β-cells: its significance for Ca2+-dependent insulin secretion from the islets of Langerhans. Endocrine 13:251–262PubMed
34.
Bas F, Darendeliler F, Demirkol D, Bundak R, Saka N, Gunoz H (1999) Successful therapy with calcium channel blocker (nifedipine) in persistent neonatal hyperinsulinemic hypoglycemia of infancy. J Pediatr Endocrinol Metab 12:873–878PubMed
35.
Eichmann D, Hufnagel M, Quick P, Santer R (1999) Treatment of hyperinsulinaemic hypoglycaemia with nifedipine. Eur J Pediatr 158:204–206CrossRefPubMed
36.
Sanke T, Nanjo K, Kondo M, Nishi M, Moriyama Y, Miyamura K (1986) Effect of calcium antagonists on reactive hypoglycemia associated with hyperinsulinemia. Metabolism 35:924–927PubMed
37.
Salkoff L (1983) Genetic and voltage-clamp analysis of a Drosophila potassium channel. Cold Spring Harb Symp Quant Biol 48 Pt 1:221–231
38.
Kamb A, Tseng-Crank J, Tanouye MA (1988) Multiple products of the Drosophila Shaker gene may contribute to potassium channel diversity. Neuron 1:421–430PubMed
39.
Pongs O, Kecskemethy N, Muller R, Krah-Jentgens I, Baumann A, Kiltz HH, Canal I, Llamazares S, Ferrus A (1988) Shaker encodes a family of putative potassium channel proteins in the nervous system of Drosophila. EMBO J 7:1087–1096PubMed
40.
Tempel BL, Papazian DM, Schwarz TL, Jan YN, Jan LY (1987) Sequence of a probable potassium channel component encoded at Shaker locus of Drosophila. Science 237:770–775PubMed
41.
Christie MJ, Adelman JP, Douglass J, North RA (1989) Expression of a cloned rat brain potassium channel in Xenopus oocytes. Science 244:221–224PubMed
42.
Tempel BL, Jan YN, Jan LY (1988) Cloning of a probable potassium channel gene from mouse brain. Nature 332:837–839CrossRefPubMed
43.
Sano Y, Mochizuki S, Miyake A et al. (2002) Molecular cloning and characterization of Kv6.3, a novel modulatory subunit for voltage-gated K+ channel Kv2.1. FEBS Lett 512:230–234CrossRefPubMed
44.
Christie MJ (1995) Molecular and functional diversity of K+ channels. Clin Exp Pharmacol Physiol 22:944–951PubMed
45.
Dilks D, Ling HP, Cockett M, Sokol P, Numann R (1999) Cloning and expression of the human Kv4.3 potassium channel. J Neurophysiol 81:1974–1977PubMed
46.
Hugnot JP, Salinas M, Lesage F et al. (1996) Kv8.1, a new neuronal potassium channel subunit with specific inhibitory properties towards Shab and Shaw channels. EMBO J 15:3322–3331PubMed
47.
Ottschytsch N, Raes A, Van Hoorick D, Snyders DJ (2002) Obligatory heterotetramerization of three previously uncharacterized Kv channel α-subunits identified in the human genome. Proc Natl Acad Sci USA 99:7986–7991CrossRefPubMed
48.
Salinas M, Duprat F, Heurteaux C, Hugnot JP, Lazdunski M (1997) New modulatory α-subunits for mammalian Shab K+ channels. J Biol Chem 272:24371–24379CrossRefPubMed
49.
Stocker M, Kerschensteiner D (1998) Cloning and tissue distribution of two new potassium channel α-subunits from rat brain. Biochem Biophys Res Commun 248:927–934CrossRefPubMed
50.
Bauer CK, Schwarz JR (2001) Physiology of EAG K+ channels. J Membr Biol 182:1–15PubMed
51.
Robbins J (2001) KCNQ potassium channels: physiology, pathophysiology, and pharmacology. Pharmacol Ther 90:1–19CrossRefPubMed
52.
MacDonald PE, Ha XF, Wang J et al. (2001) Members of the Kv1 and Kv2 voltage-dependent K+ channel families regulate insulin secretion. Mol Endocrinol 15:1423–1435PubMed
53.
Tamarina NA, Kuznetsov A, Dukes ID, Philipson LH (2002) Delayed rectifier potassium channel Kv2.1 role in β-cell physiology and insulin secretion. Diabetes 51:P1525 (abstract)
54.
MacDonald PE, Salapatek AMF, Wheeler MB (2002) Glucagon-like peptide-1 receptor activation antagonizes voltage-dependent repolarizing K+ currents in β-cells: A possible glucose-dependent insulinotropic mechanism. Diabetes 51:S443–S447PubMed
55.
MacDonald PE, Wang G, Tsuk S et al. (2002) Synaptosome-associated protein of 25 kilodaltons modulates Kv2.1 voltage-dependent K+ channels in neuroendocrine islet β-cells through an interaction with the channel N-terminus. Mol Endocrinol 16:2452–2461CrossRefPubMed
56.
MacDonald PE, Salapatek AMF, Wheeler MB (2003) Temperature and redox state dependence of native Kv2.1 currents in rat pancreatic β-cells. J Physiol 546:647–653CrossRefPubMed
57.
Dean PM, Matthews EK (1970) Glucose-induced electrical activity in pancreatic islet cells. J Physiol 210:255–264PubMed
58.
Pace CS, Price S (1972) Electrical responses of pancreatic islet cells to secretory stimuli. Biochem Biophys Res Commun 46:1557–1563PubMed
59.
Hodgkin AL, Huxley AF (1952) Currents carried by sodium and potassium ions through the membrane of the gian axon of Loligo. J Physiol (Lond) 116:449–472
60.
Hodgkin AL, Huxley AF (1952) The components of membrane conductance in the giant axon of Loligo. J Physiol (Lond) 116:473–496
61.
Atwater I, Ribalet B, Rojas E (1979) Mouse pancreatic β-cells: tetraethylammonium blockage of the potassium permeability increase induced by depolarization. J Physiol (Lond) 288:561–574
62.
Henquin JC (1977) Tetraethylammonium potentiation of insulin release and inhibition of rubidium efflux in pancreatic islets. Biochem Biophys Res Commun 77:551–556PubMed
63.
Henquin JC (1990) Role of voltage- and Ca2+-dependent K+ channels in the control of glucose-induced electrical activity in pancreatic β-cells. Pflugers Arch 416:568–572PubMed
64.
Philipson LH, Rosenberg MP, Kuznetsov A, Lancaster ME, Worley JF III, Roe MW, Dukes ID (1994) Delayed rectifier K+ channel overexpression in transgenic islets and β-cells associated with impaired glucose responsiveness. J Biol Chem 269:27787–27790PubMed
65.
Eberhardson M, Tengholm A, Grapengiesser E (1996) The role of plasma membrane K+ and Ca2+ permeabilities for glucose induction of slow Ca2+ oscillations in pancreatic β-cells. Biochim Biophys Acta 1283:67–72CrossRefPubMed
66.
Roe MW, Worley JF III, Mittal AA et al. (1996) Expression and function of pancreatic β-cell delayed rectifier K+ channels. Role in stimulus-secretion coupling. J Biol Chem 271:32241–32246CrossRefPubMed
67.
Gopel SO, Kanno T, Barg S, Eliasson L, Galvanovskis J, Renstrom E, Rorsman P (1999) Activation of Ca2+-dependent K+ channels contributes to rhythmic firing of action potentials in mouse pancreatic β cells. J Gen Physiol 114:759–770CrossRefPubMed
68.
Creutzfeldt W (2001) The entero-insular axis in type 2 diabetes-incretins as therapeutic agents. Exp Clin Endocrinol Diabetes 109 [Suppl 2]:S288–S303
69.
Efanov AM, Zaitsev SV, Mest HJ et al. (2001) The novel imidazoline compound BL11282 potentiates glucose-induced insulin secretion in pancreatic β-cells in the absence of modulation of KATP channel activity. Diabetes 50:797–802PubMed
70.
Morgan NG, Chan SL, Mourtada M, Monks LK, Ramsden CA (1999) Imidazolines and pancreatic hormone secretion. Ann NY Acad Sci 881:217–228PubMed
71.
Hashiguchi S, Yada T, Arima T (2001) A new hypoglycemic agent, JTT-608, evokes protein kinase A-mediated Ca2+ signaling in rat islet β-cells: strict regulation by glucose, link to insulin release, and cooperation with glucagon-like peptide-1 (7–36) amide and pituitary adenylate cyclase-activating polypeptide. J Pharmacol Exp Ther 296:22–30PubMed
72.
Bokvist K, Rorsman P, Smith PA (1990) Effects of external tetraethylammonium ions and quinine on delayed rectifying K+ channels in mouse pancreatic β-cells. J Physiol (Lond) 423:311–325
73.
Gopel S, Kanno T, Barg S, Galvanovskis J, Rorsman P (1999) Voltage-gated and resting membrane currents recorded from β-cells in intact mouse pancreatic islets. J Physiol 521 Pt 3:717–728
74.
Smith PA, Bokvist K, Arkhammar P, Berggren PO, Rorsman P (1990) Delayed rectifying and calcium-activated K+ channels and their significance for action potential repolarization in mouse pancreatic β-cells. J Gen Physiol 95:1041–1059PubMed
75.
Su J, Yu H, Lenka N, Hescheler J, Ullrich S (2001) The expression and regulation of depolarization-activated K+ channels in the insulin-secreting cell line INS-1. Pflugers Arch 442:49–56CrossRefPubMed
76.
Best L (2002) Evidence that glucose-induced electrical activity in rat pancreatic β-cells does not require KATP channel inhibition. J Membr Biol 185:193–200PubMed
77.
Ahren B, Leander S, Lundquist I (1981) Effects of 4-aminopyridine on insulin secretion and plasma glucose levels in intact and adrenalectomized-chemically sympathectomized mice. Eur J Pharmacol 74:221–226CrossRefPubMed
78.
Ruppersberg JP, Stocker M, Pongs O, Heinemann SH, Frank R, Koenen M (1991) Regulation of fast inactivation of cloned mammalian IKA channels by cysteine oxidation. Nature 352:711–714PubMed
79.
Walaas SI, Greengard P (1991) Protein phosphorylation and neuronal function. Pharmacol Rev 43:299–349PubMed
80.
Archer SL, Souil E, Dinh-Xuan AT et al. (1998) Molecular identification of the role of voltage-gated K+ channels, Kv1.5 and Kv2.1, in hypoxic pulomnary vasoconstriction and control of resting membrane potential in rat pulmonary artery myocytes. J Clin Invest 101:2319–2330PubMed
81.
Smith PA, Bokvist K, Rorsman P (1989) Demonstration of A-currents in pancreatic islet cells. Pflugers Arch 413:441–443PubMed
82.
Gopel SO, Kanno T, Barg S, Rorsman P (2000) Patch-clamp characterisation of somatostatin-secreting δ-cells in intact mouse pancreatic islets. J Physiol 528:497–507PubMed
83.
Ji J, Tsuk S, Salapatek AMF, Huang X et al. (2002) The 25-kDa synaptosome associated protein (SNAP-25) binds and inhibits delayed rectifier potassium channels in secretory cells. J Biol Chem 277:20195–20204CrossRefPubMed
84.
Fatherazi S, Cook DL (1991) Specificity of tetraethylammonium and quinine for three K channels in insulin-secreting cells. J Membr Biol 120:105–114PubMed
85.
Li ZW, Ding JP, Kalyanaraman V, Lingle CJ (1999) RINm5f cells express inactivating BK channels whereas HIT cells express noninactivating BK channels. J Neurophysiol 81:611–624PubMed
86.
Oosawa Y, Ashcroft SJ, Ashcroft FM (1992) Ca2+-activated K+ channels from an insulin-secreting cell line incorporated into planar lipid bilayers. Diabetologia 35:619–623PubMed
87.
Ammala C, Bokvist K, Larsson O, Berggren PO, Rorsman P (1993) Demonstration of a novel apamin-insensitive calcium-activated K+ channel in mouse pancreatic β-cells. Pflugers Arch 422:443–448PubMed
88.
Kozak JA, Misler S, Logothetis DE (1998) Characterization of a Ca2+-activated K+ current in insulin-secreting murine βTC-3 cells. J Physiol (Lond) 509 (Pt 2):355–370
89.
Kukuljan M, Goncalves AA, Atwater I (1991) Charybdotoxin-sensitive KCa channel is not involved in glucose-induced electrical activity in pancreatic β-cells. J Membr Biol 119:187–195PubMed
90.
Lebrun P, Malaisse WJ, Herchuelz A (1983) Activation, but not inhibition, by glucose of Ca2+-dependent K+ permeability in the rat pancreatic β-cell. Biochim Biophys Acta 731:145–150CrossRefPubMed
91.
92.
Philipson LH, Hice RE, Schaefer K, LaMendola J, Bell GI, Nelson DJ, Steiner DF (1991) Sequence and functional expression in Xenopus oocytes of a human insulinoma and islet potassium channel. Proc Natl Acad Sci USA 88:53–57PubMed
93.
Chouinard SW, Lu F, Ganetzky B, MacDonald MJ (2000) Evidence for voltage-gated potassium channel β-subunits with oxidoreductase motifs in human and rodent pancreatic β cells. Recept Channels 7:237–243PubMed
94.
Rosati B, Marchetti P, Crociani O, Lecchi M, Lupi R, Arcangeli A, Olivotto M, Wanke E (2000) Glucose- and arginine-induced insulin secretion by human pancreatic β-cells: the role of HERG K+ channels in firing and release. FASEB J 14:2601–2610CrossRefPubMed
95.
Kalman K, Nguyen A, Tseng-Crank J, Dukes ID, Chandy G, Hustad CM, Copeland NG, Jenkins NA, Mohrenweiser H, Brandriff B, Cahalan M, Gutman GA, Chandy KG (1998) Genomic organization, chromosomal localization, tissue distribution, and biophysical characterization of a novel mammalian Shaker-related voltage-gated potassium channel, Kv1.7. J Biol Chem 273:5851–5857PubMed
96.
97.
Chandra J, Zhivotovsky B, Zaitsev S, Juntti-Berggren L, Berggren PO, Orrenius S (2001) Role of apoptosis in pancreatic β-cell death in diabetes. Diabetes 50 [Suppl 1]:S44–S47
98.
Xu J, Koni PA, Wang P et al. (2003) The voltage-gated potassium channel Kv1.3 regulates energy homeostasis and body weight. Hum Mol Genet 12:551–559CrossRefPubMed
99.
Liu Y, Gutterman DD (2002) The coronary circulation in diabetes: influence of reactive oxygen species on K+ channel-mediated vasodilation. Vascul Pharmacol 38:43–49CrossRefPubMed
100.
Cahalan MD, Chandy KG (1997) Ion channels in the immune system as targets for immunosuppression. Curr Opin Biotechnol 8:749–756CrossRefPubMed
101.
Nilius B, Wohlrab W (1992) Potassium channels and regulation of proliferation of human melanoma cells. J Physiol 445:537–548PubMed
102.
Zhou Q, Kwan HY, Chan HC, Jiang JL, Tam SC, Yao X (2003) Blockage of voltage-gated K+ channels inhibits adhesion and proliferation of hepatocarcinoma cells. Int J Mol Med 11:261–266PubMed
103.
Rouzaire-Dubois B, DuBois JM (1998) K+ channel block-induced mammalian neuroblastoma cell swelling: a possible mechanism to influence proliferation. J Physiol 510 (Pt 1):93–102PubMed
104.
Salinas M, Weille J de, Guillemare E, Lazdunski M, Hugnot JP (1997) Modes of regulation of shab K+ channel activity by the Kv8.1 subunit. J Biol Chem 272:8774–8780CrossRefPubMed
105.
Post MA, Kirsch GE, Brown AM (1996) Kv2.1 and electrically silent Kv6.1 potassium channel subunits combine and express a novel current. FEBS Lett 399:177–182CrossRefPubMed
106.
Kerschensteiner D, Stocker M (1999) Heteromeric assembly of Kv2.1 with Kv9.3: effect on the state dependence of inactivation. Biophys J 77:248–257PubMed
107.
Kramer JW, Post MA, Brown AM, Kirsch GE (1998) Modulation of potassium channel gating by coexpression of Kv2.1 with regulatory Kv5.1 or Kv6.1 alpha-subunits. Am J Physiol 274:C1501–C1510PubMed
108.
Patel AJ, Lazdunski M, Honore E (1997) Kv2.1/Kv9.3, a novel ATP-dependent delayed-rectifier K+ channel in oxygen-sensitive pulmonary artery myocytes. EMBO J 16:6615–6625CrossRefPubMed
109.
Pongs O, Leicher T, Berger M, Roeper J, Bahring R, Wray D, Giese KP, Silva AJ, Storm JF (1999) Functional and molecular aspects of voltage-gated K+ channel β-subunits. Ann NY Acad Sci 868:344–355PubMed
110.
Heinemann SH, Rettig J, Graack HR, Pongs O (1996) Functional characterization of Kv channel β-subunits from rat brain. J Physiol (Lond) 493:625–633
111.
Rhodes KJ, Keilbaugh SA, Barrezueta NX, Lopez KL, Trimmer JS (1995) Association and colocalization of K+ channel α- and β-subunit polypeptides in rat brain. J Neurosci 15:5360–5371PubMed
112.
Trimmer JS (1991) Immunological idendification and characteriazation of a delayed rectifier K+ channel polypeptide in rat brain. Proc Natl Acad Sci USA 88:10764–10768PubMed
113.
Wible BA, Yang Q, Kuryshev YA, Accili EA, Brown AM (1998) Cloning and expression of a novel K+ channel regulatory protein, KChAP. J Biol Chem 273:11745–11751PubMed
114.
Coppock EA, Martens JR, Tamkun MM (2001) Molecular basis of hypoxia-induced pulmonary vasoconstriction: role of voltage-gated K+ channels. Am J Physiol Lung Cell Mol Physiol 281:L1–L12PubMed
115.
Klumpp DJ, Song EJ, Pinto LH (1995) Identification and localization of K+ channels in the mouse retina. Vis Neurosci 12:1177–1190PubMed
116.
Maletic-Savatic M, Lenn NJ, Trimmer JS (1995) Differential spatiotemporal expression of K+ channel polypeptides in rat hippocampal neurons developing in situ and in vitro. J Neurosci 15:3840–3851PubMed
117.
Scannevin RH, Murakoshi H, Rhodes KJ, Trimmer JS (1996) Identification of a cytoplasmic domain important in the polarized expression and clustering of the Kv2.1 K+ channel. J Cell Biol 135:1619–1632PubMed
118.
Lim ST, Antonucci DE, Scannevin RH, Trimmer JS (2000) A novel targeting signal for proximal clustering of the Kv2.1 K+ channel in hippocampal neurons. Neuron 25:385–397PubMed
119.
Martens JR, Navarro-Polanco R, Coppock EA, Nishiyama A, Parshley L, Grobaski TD, Tamkun MM (2000) Differential targeting of Shaker-like potassium channels to lipid rafts. J Biol Chem 275:7443–7446CrossRefPubMed
120.
Martens JR, Sakamoto N, Sullivan SA, Grobaski TD, Tamkun MM (2001) Isoform-specific localization of voltage-gated K+ channels to distinct lipid raft populations. Targeting of Kv1.5 to caveolae. J Biol Chem 276:8409–8414CrossRefPubMed
121.
Shi G, Kleinklaus AK, Marrion NV, Trimmer JS (1994) Properties of Kv2.1 K+ channels expressed in transfected mammalian cells. J Biol Chem 269:23204–23211PubMed
122.
Shi G, Trimmer JS (1999) Differential asparagine-linked glycosylation of voltage-gated K+ channels in mammalian brain and in transfected cells. J Membr Biol 168:265–273CrossRefPubMed
123.
Frech GC, VanDongen AM, Schuster G, Brown AM, Joho RH (1989) A novel potassium channel with delayed rectifier properties isolated from rat brain by expression cloning. Nature 340:642–645
124.
Sharma N, D'Arcangelo G, Kleinlaus A, Halegoua S, Trimmer JS (1993) Nerve growth factor regulates the abundance and distribution of K+ channels in PC12 cells. J Cell Biol 123:1835–1843PubMed
125.
Belevych AE, Beck R, Tammaro P, Poston L, Smirnov SV (2002) Developmental changes in the functional characteristics and expression of voltage-gated K+ channel currents in rat aortic myocytes. Cardiovasc Res 54:152–161CrossRefPubMed
126.
Barry DM, Trimmer JS, Merlie JP, Nerbonne JM (1995) Differential expression of voltage-gated K+ channel subunits in adult rat heart. Relation to functional K+ channels? Circ Res 77:361–369
127.
Huang B, Qin D, El Sherif N (2001) Spatial alterations of Kv channels expression and K+ currents in post-MI remodeled rat heart. Cardiovasc Res 52:246–254CrossRefPubMed
128.
Xu C, Lu Y, Tang G, Wang R (1999) Expression of voltage-dependent K+ channel genes in mesenteric artery smooth muscle cells. Am J Physiol 277:G1055–G1063PubMed
129.
Murakoshi H, Shi G, Scannevin RH, Trimmer JS (1997) Phosphorylation of the Kv2.1 K+ channel alters voltage-dependent activation. Mol Pharmacol 52:821–828PubMed
130.
Gerber SH Sudhof TC (2002) Molecular determinants of regulated exocytosis. Diabetes 51:S3–S11PubMed
131.
Wiser O, Bennet MK, Atlas D (1996) Functional interaction of syntaxin and SNAP-25 with voltage-sensitive L- and N-type Ca2+ channels. EMBO J 15:4100–4110PubMed
132.
Wiser O, Trus M, Hernandez A, Renstrom E, Barg S, Rorsman P, Atlas D (1999) The voltage sensitive Lc-type Ca2+ channel is functionally coupled to the exocytotic machinery. Proc Natl Acad Sci USA 96:248–253CrossRefPubMed
133.
Barg S, Ma X, Eliasson L et al. (2001) Fast exocytosis with few Ca2+ channels in insulin-secreting mouse pancreatic β-cells. Biophys J 81:3308–3323PubMed
134.
Fili O, Michaelevski I, Bledi Y et al. (2001) Direct interaction of a brain voltage-gated K+ channel with syntaxin 1A: functional impact on channel gating. J Neurosci 21:1964–1974PubMed
135.
Ji J, Salapatek AM, Lau H, Wang G, Gaisano HY, Diamant NE (2002) SNAP-25, a SNARE protein, inhibits two types of K channels in esophageal smooth muscle. Gastroenterology 122:994–1006PubMed
136.
Leung YM, Kang Y, Gao X et al. (2003) Syntaxin 1A binds to the cytoplasmic C-terminus of Kv2.1 to regulate channel gating and trafficking. J Biol Chem 278:17532–17538CrossRefPubMed
137.
Soliven B, Nelson DJ (1990) β-adrenergic modulation of K+ current in human T lymphocytes. J Membr Biol 117:263–274PubMed
138.
Walsh KB, Begenisich TB, Kass RS (1989) β-adrenergic modulation of cardiac ion channels. Differential temperature sensitivity of potassium and calcium currents. J Gen Physiol 93:841–854PubMed
139.
Choquet D, Sarthou P, Primi D, Cazenave PA, Korn H (1987) Cyclic AMP-modulated potassium channels in murine B cells and their precursors. Science 235:1211–1214PubMed
140.
Walsh KB, Kass RS (1988) Regulation of a heart potassium channel by protein kinase A and C. Science 242:67–69PubMed
141.
Chung S, Kaczmarek LK (1995) Modulation of the inactivation of voltage-dependent potassium channels by cAMP. J Neurosci 15:3927–3935PubMed
142.
Duchatelle-Gourdon I, Hartzell HC (1990) Single delayed rectifier channels in frog atrial cells. Effects of β-adrenergic stimulation. Biophys J 57:903–909PubMed
143.
Perozo E, Vandenberg CA, Jong DS, Bezanilla F (1991) Single channel studies of the phosphorylation of K+ channels in the squid giant axon. I. Steady-state conditions. J Gen Physiol 98:1–17PubMed
144.
Huang XY, Morielli AD, Peralta EG (1994) Molecular basis of cardiac potassium channel stimulation by protein kinase A. Proc Natl Acad Sci USA 91:624–628PubMed
145.
Levin G, Chikvashvili D, Singer-Lahat D, Peretz T, Thornhill WB, Lotan I (1996) Phosphorylation of a K+ channel α-subunit modulates the inactivation conferred by a β-subunit. Involvement of cytoskeleton. J Biol Chem 271:29321–29328CrossRefPubMed
146.
Kwak YG, Hu NN, Wei J et al. (1999) Protein kinase A phosphorylation alters Kvβ1.3 subunit-mediated inactivation of the Kv1.5 potassium channel. J Biol Chem 274:13928–13932CrossRefPubMed
147.
Potet F, Scott JD, Mohammad-Panah R, Escande D, Baro I (2001) AKAP proteins anchor cAMP-dependent protein kinase to KvLQT1/IsK channel complex. Am J Physiol Heart Circ Physiol 280:H2038–H2045PubMed
148.
Fournier L, Whitfield JF, Xiang H, Schwartz JL, Begin-Heick N (1993) K+ channel and α2-adrenergic effects on glucose-induced Ca2+ i surges: aberrant behavior in ob/ob mice. Am J Physiol 264:C1458–C1465PubMed
149.
Wilson GG, O'Neill CA, Sivaprasadarao A, Findlay JB, Wray D (1994) Modulation by protein kinase A of a cloned rat brain potassium channel expressed in Xenopus oocytes. Pflugers Arch 428:186–193PubMed
150.
Boland LM, Jackson KA (1999) Protein kinase C inhibits Kv1.1 potassium channel function. Am J Physiol 277:C100–C110PubMed
151.
Murray KT, Fahrig SA, Deal KK et al. (1994) Modulation of an inactivating human cardiac K+ channel by protein kinase C. Circ Res 75:999–1005PubMed
152.
Conley EC (1999) VLG K Kv1-Shak. In: Conley EC, Brammar WJ (eds) The ion channel facts book IV: voltage-gated channels. Academic Press, London, pp 347–523
153.
MacDonald PE, El-kholy W, Riedel MJ, Salapatek AMF, Light PE, Wheeler MB (2002) The multiple actions of GLP-1 on the process of glucose-stimulated insulin secretion. Diabetes 51:S434–S442PubMed
154.
Dukes ID, Philipson LH (1996) K+ channels: generating excitement in pancreatic β-cells. Diabetes 45:845–853PubMed
155.
Gulbis JM, Mann S, MacKinnon R (1999) Structure of a voltage-dependent K+ channel β-subunit. Cell 97:943–952PubMed
156.
Chouinard SW, Wilson GF, Schlimgen AK, Ganetzky B (1995) A potassium channel β-subunit related to the aldo-keto reductase superfamily is encoded by the Drosophila hyperkinetic locus. Proc Natl Acad Sci USA 92:6763–6767PubMed
157.
McCormack T, McCormack K (1994) Shaker K+ channel β-subunits belong to an NAD(P)H-dependent oxidoreductase superfamily. Cell 79:1133–1135PubMed
158.
Peri R, Wible BA, Brown AM (2001) Mutations in the Kvβ2 binding site for NADPH and their effects on Kv1.4. J Biol Chem 276:738–741CrossRefPubMed
159.
Bahring R, Milligan CJ, Vardanyan V et al. (2001) Coupling of voltage-dependent potassium channel inactivation and oxidoreductase active site of Kvβ subunits. J Biol Chem 276:22923–22929CrossRefPubMed
160.
Campomanes CR, Carroll KI, Manganas LN et al. (2002) Kv β-subunit oxidoreductase activity and Kv1 potassium channel trafficking. J Biol Chem 277:8298–8305CrossRefPubMed
161.
Archer SL, Will JA, Weir EK (1986) Redox status in the control of pulmonary vascular tone. Herz 11:127–141PubMed
162.
MacDonald MJ (1995) Feasibility of a mitochondrial pyruvate malate shuttle in pancreatic islets. Further implication of cytosolic NADPH in insulin secretion. J Biol Chem 270:20051–20058PubMed
163.
Fahien LA, MacDonald MJ (2002) The succinate mechanism of insulin release. Diabetes 51:2669–2676PubMed
164.
MacDonald MJ (2003) The export of metabolites from mitochondria and anaplerosis in insulin secretion. Biochim Biophys Acta 1619:77–88CrossRefPubMed
165.
Lu D, Mulder H, Zhao P et al. (2002) 13C NMR isotopomer analysis reveals a connection between pyruvate cycling and glucose-stimulated insulin secretion (GSIS). Proc Natl Acad Sci USA 99:2708–2713CrossRefPubMed
166.
Ashcroft SJ, Christie MR (1979) Effects of glucose on the cytosolic ration of reduced/oxidized nicotinamide-adenine dinucleotide phosphate in rat islets of Langerhans. Biochem J 184:697–700PubMed
167.
Hedeskov CJ, Capito K, Thams P (1987) Cytosolic ratios of free [NADPH]/[NADP+] and [NADH]/[NAD+] in mouse pancreatic islets, and nutrient-induced insulin secretion. Biochem J 241:161–167PubMed
168.
Ammon HP, Steinke J (1972) 6-Amnionicotinamide (6-AN) as a diabetogenic agent. In vitro and in vivo studies in the rat. Diabetes 21:143–148PubMed
169.
MacDonald MJ, Ammon HP, Patel T, Steinke J (1974) Failure of 6-aminonicotinamide to inhibit the potentiating effect of leucine and arginine on glucose-induced insulin release in vitrol. Diabetologia 10:761–765PubMed
170.
Laclau M, Lu F, MacDonald MJ (2001) Enzymes in pancreatic islets that use NADP(H) as a cofactor including evidence for a plasma membrane aldehyde reductase. Mol Cell Biochem 225:151–160CrossRefPubMed
171.
Kizer JS, Vargas-Gordon M, Brendel K, Bressler R (1970) The in vitro inhibition of insulin secretion by diphenylhydantoin. J Clin Invest 49:1942–1948PubMed
172.
Levin SR, Grodsky GM, Hagura R, Smith D (1972) Comparison of the inhibitory effects of diphenylhydantoin and diazoxide upon insulin secretion from the isolated perfused pancreas. Diabetes 21:856–862PubMed
173.
Matthews EK, Sakamoto Y (1975) Pancreatic islet cells: electrogenic and electrodiffusional control of membrane potential. J Physiol 246:439–457PubMed
174.
Misler S, Barnett DW, Gillis KD, Pressel DM (1992) Electrophysiology of stimulus-secretion coupling in human β-cells. Diabetes 41:1221–1228PubMed
175.
Michelakis ED, Rebeyka I, Wu X et al. (2002) O2 sensing in the human ductus arteriosus: regulation of voltage-gated K+ channels in smooth muscle cells by a mitochondrial redox sensor. Circ Res 91:478–486CrossRefPubMed
176.
Henquin JC (1998) A minimum of fuel is necessary for tolbutamide to mimic the effects of glucose on electrical activity in pancreatic β-cells. Endocrinology 139:993–998PubMed
177.
Smith PA, Rorsman P, Ashcroft FM (1989) Modulation of dihydropyridine-sensitive Ca2+ channels by glucose metabolism in mouse pancreatic β-cells. Nature 342:550–553PubMed
178.
Owada S, Larsson O, Arkhammar P et al. (1999) Glucose decreases Na+/K+-ATPase activity in pancreatic β-cells. An effect mediated via Ca2+-independent phospholipase A2 and protein kinase C-dependent phosphorylation of the α-subunit. J Biol Chem 274:2000–2008CrossRefPubMed
179.
Betsholtz C, Baumann A, Kenna S et al. (1990) Expression of voltage-gated K+ channels in insulin-producing cells. Analysis by polymerase chain reaction. FEBS Lett 263:121–126CrossRefPubMed
Metadata
Title
Voltage-dependent K+ channels in pancreatic beta cells: Role, regulation and potential as therapeutic targets
Authors
Dr. P. E. MacDonald
M. B. Wheeler
Publication date
01-08-2003
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 8/2003
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-003-1159-8

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