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Regulation of Insulin Secretion in Islets of Langerhans by Ca2+Channels

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Abstract

Insulin secretion from β-cells of the pancreatic islets of Langerhans is triggered by Ca2+ influx through voltage-dependent Ca2+ channels. Electrophysiological and molecular studies indicate that β-cells express several subtypes of these channels. This review discusses their roles in regulating insulin secretion, focusing on recent studies using β-cells, exogenous expression systems, and Ca2+ channel knockout mice. These investigations reveal that L-type Ca2+ channels in the β-cell physically interact with the secretory apparatus by binding to synaptic proteins on the plasma membrane and insulin granule. As a result, Ca2+ influx through L-type channels efficiently and rapidly stimulates release of a pool of insulin granules in close contact with the channels. Thus, L-type Ca2+ channel activity is preferentially coupled to exocytosis in the β-cell, and plays a critical role in regulating the dynamics of insulin secretion. Non-L-type channels carry a significant portion of the total voltage-dependent Ca2+ current in β-cells and cell lines from some species, but nevertheless account for only a small fraction of insulin secretion. These channels may regulate exocytosis indirectly by affecting membrane potential or second messenger signaling pathways. Finally, voltage-independent Ca2+ entry pathways and their potential roles in β-cell function are discussed. The emerging picture is that Ca2+ channels regulate insulin secretion at multiple sites in the stimulus-secretion coupling pathway, with the specific role of each channel determined by its biophysical and structural properties.

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References

  1. C. Ämmälä L. Eliasson K. Bokvist O. Larsson F.M. Ashcroft P. Rorsman (1993) ArticleTitleExocytosis elicited by action potentials and voltage-clamp calcium currents in individual mouse pancreatic β-cells J. Physiol. 472 665–688 Occurrence Handle8145165

    PubMed  Google Scholar 

  2. F.M. Ashcroft P. Rorsman (1989) ArticleTitleElectrophysiology of the pancreatic β-cell Prog. Biophys. Mol. Biol. 54 87–143 Occurrence Handle10.1016/0079-6107(89)90013-8 Occurrence Handle1:STN:280:By6B38jltl0%3D Occurrence Handle2484976

    Article  CAS  PubMed  Google Scholar 

  3. D. Atlas (2001) ArticleTitleFunctional and physical coupling of voltage-sensitive calcium channels with exocytotic proteins: ramifications for the secretion mechanism J. Neurochem. 77 972–985 Occurrence Handle10.1046/j.1471-4159.2001.00347.x Occurrence Handle1:CAS:528:DC%2BD3MXktVWitro%3D Occurrence Handle11359862

    Article  CAS  PubMed  Google Scholar 

  4. R.M. Barbosa A.M. Silva A.R. Tome J.A. Stamford R.M. Santos L.M. Rosario (1998) ArticleTitleControl of pulsatile 5-HT/insulin secretion from single mouse pancreatic islets by intracellular calcium dynamics J. Physiol. 510 135–143 Occurrence Handle10.1111/j.1469-7793.1998.135bz.x Occurrence Handle1:CAS:528:DyaK1cXkvVKks70%3D Occurrence Handle9625872

    Article  CAS  PubMed  Google Scholar 

  5. S. Barg (2003) ArticleTitleMechanisms of exocytosis in insulin-secreting β-cells and glucagon-secreting α-cells Pharmacol. Toxicol. 92 3–13 Occurrence Handle10.1034/j.1600-0773.2003.920102.x Occurrence Handle1:CAS:528:DC%2BD3sXitlCrurs%3D Occurrence Handle12710591

    Article  CAS  PubMed  Google Scholar 

  6. S. Barg L. Eliasson E. Renstrom P. Rorsman (2002) ArticleTitleA subset of 50 secretory granules in close contact with L-type Ca2+ channels accounts for first-phase insulin secretion in mouse β-cells Diabetes 51 S74–82 Occurrence Handle1:CAS:528:DC%2BD38XhtVaqs7o%3D Occurrence Handle11815462

    CAS  PubMed  Google Scholar 

  7. S. Barg X. Ma L. Eliasson J. Galvanovskis S.O. Gopel S. Obermuller J. Platzer E. Renstrom M. Trus D. Atlas J. Striessnig P. Rorsman (2001) ArticleTitleFast exocytosis with few Ca2+ channels in insulin-secreting mouse pancreatic β-cells Biophys. J. 81 3308–3323 Occurrence Handle1:CAS:528:DC%2BD3MXovVemsbk%3D Occurrence Handle11720994

    CAS  PubMed  Google Scholar 

  8. E. Bernal-Mizrachi B. Wice H. Inoue M.A. Permutt (2000) ArticleTitleActivation of serum response factor in the depolarization induction of Egr-1 transcription in pancreatic islet β-cells J. Biol. Chem. 275 25681–25689 Occurrence Handle10.1074/jbc.M003424200 Occurrence Handle1:CAS:528:DC%2BD3cXmtVehtrY%3D Occurrence Handle10829028

    Article  CAS  PubMed  Google Scholar 

  9. R. Bertram J. Previte A. Sherman T.A. Kinard L.S. Satin (2000) ArticleTitleThe phantom burster model for pancreatic beta-cells Biophys. J. 79 2880–2892 Occurrence Handle1:CAS:528:DC%2BD3MXitFWr Occurrence Handle11106596

    CAS  PubMed  Google Scholar 

  10. R. Bertram P. Smolen A. Sherman D. Mears I. Atwater F. Martin B. Soria (1995) ArticleTitleA role for calcium release-activated current (CRAC) in cholinergic modulation of electrical activity in pancreatic β-cells Biophys. J. 68 2323–2332 Occurrence Handle1:CAS:528:DyaK2MXlvFOmtL4%3D Occurrence Handle7647236

    CAS  PubMed  Google Scholar 

  11. K. Bokvist L. Eliasson C. Ammala E. Renstrom P. Rorsman (1995) ArticleTitleCo-localization of L-type Ca2+ channels and insulin-containing secretory granules and its significance for the initiation of exocytosis in mouse pancreatic β-cells EMBO J. 14 50–57 Occurrence Handle1:CAS:528:DyaK2MXjt1yqtbw%3D Occurrence Handle7828595

    CAS  PubMed  Google Scholar 

  12. W.A. Catterall J. Striessnig T.P. Snutch E. Perez-Reyes (2003) ArticleTitleInternational Union of Pharmacology. XL. Compendium of voltage-gated ion channels: calcium channels Pharmacol. Rev. 55 579–581 Occurrence Handle10.1124/pr.55.4.8 Occurrence Handle1:CAS:528:DC%2BD2cXhtlWktw%3D%3D Occurrence Handle14657414

    Article  CAS  PubMed  Google Scholar 

  13. E. Cerasi (1992) Aetiology of type II diabetes F.M. Ashcroft (Eds) Insulin—Molecular Biology to Pathology. IRL Oxford, U.K. 352–392

    Google Scholar 

  14. D.E. Clapham C. Montell G. Schultz D. Julius (2003) ArticleTitleInternational Union of Pharmacology. XLIII. Compendium of voltage-gated ion channels: transient receptor potential channels Pharmacol. Rev. 55 591–596 Occurrence Handle10.1124/pr.55.4.6 Occurrence Handle14657417

    Article  PubMed  Google Scholar 

  15. D.L. Cook C.N. Hales (1984) ArticleTitleIntracellular ATP directly blocks K+ channels in pancreatic β-cells Nature 311 271–273 Occurrence Handle1:CAS:528:DyaL2cXls1yhsL0%3D Occurrence Handle6090930

    CAS  PubMed  Google Scholar 

  16. D.L. Cook L.S. Satin W.F. Hopkins (1991) ArticleTitlePancreatic β-cells are bursting, but how? Trends Neurosci. 14 411–414 Occurrence Handle1:CAS:528:DyaK3MXmt12iur8%3D

    CAS  Google Scholar 

  17. P.M. Dean E.K. Matthews (1968) ArticleTitleElectrical activity in pancreatic islet cells Nature 219 389–390 Occurrence Handle1:STN:280:CCeA38nktlU%3D Occurrence Handle4873864

    CAS  PubMed  Google Scholar 

  18. P. Gilon R.M. Shepherd J.C. Henquin (1993) ArticleTitleOscillations of secretion driven by oscillations of cytoplasmic Ca2+ as eviden- ced in single pancreatic islets J. Biol. Chem. 268 22265–22268 Occurrence Handle1:CAS:528:DyaK3sXlslCmsrc%3D Occurrence Handle8226733

    CAS  PubMed  Google Scholar 

  19. P. Gilon J. Yakel J. Gromada Y. Zhu J.C. Henquin P. Rorsman (1997) ArticleTitleG protein-dependent inhibition of L-type Ca2+ currents by acetylcholine in mouse pancreatic β-cells J. Physiol. 499 65–76 Occurrence Handle1:CAS:528:DyaK2sXhvFenu7o%3D Occurrence Handle9061640

    CAS  PubMed  Google Scholar 

  20. H. Grabsch A. Pereverzev M. Weiergraber M. Schramm M. Henry R. Vajna R.E. Beattie S.G. Volsen U. Klockner J. Hescheler T. Schneider (1999) ArticleTitleImmunohistochemical detection of alpha1E voltage-gated Ca2+ channel isoforms in cerebellum, INS-1 cells, and neuroendocrine cells of the digestive system J. Histochem. Cytochem. 47 981–994 Occurrence Handle1:CAS:528:DyaK1MXltFWqsLw%3D Occurrence Handle10424882

    CAS  PubMed  Google Scholar 

  21. O.P. Hamill A. Marty E. Neher B. Sakmann F.J. Sigworth (1981) ArticleTitleImproved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches Pfluegers Arch. 391 85–100 Occurrence Handle10.1007/BF00656997 Occurrence Handle1:STN:280:Bi2D3sjhvVw%3D

    Article  CAS  Google Scholar 

  22. J.C. Henquin H.P. Meissner (1984) ArticleTitleSignificance of ionic fluxes and changes in membrane potential for stimulus-secretion coupling in pancreatic β-cells Experientia. 40 1043–1052 Occurrence Handle1:CAS:528:DyaL2MXptlCnsQ%3D%3D Occurrence Handle6386515

    CAS  PubMed  Google Scholar 

  23. A. Horvath G. Szabadkai P. Varnai T. Aranyi C.B. Wollheim A. Spat P. Enyedi (1998) ArticleTitleVoltage dependent calcium channels in adrenal glomerulosa cells and in insulin producing cells Cell Calcium 23 33–42 Occurrence Handle10.1016/S0143-4160(98)90072-0 Occurrence Handle1:CAS:528:DyaK1cXis1aqu7o%3D Occurrence Handle9570008

    Article  CAS  PubMed  Google Scholar 

  24. L. Huang A. Bhattacharjee J.T. Taylor M. Zhang B.M. Keyser L. Marrero M. Li (2004) ArticleTitle[Ca2+]i regulates trafficking of Cav1.3 (α1D Ca2+ channel) in insulin secreting cells Am. J. Physiol. 286 C213–C221 Occurrence Handle10.1152/ajpcell.00346.2003 Occurrence Handle1:CAS:528:DC%2BD2cXhsFarsr4%3D

    Article  CAS  Google Scholar 

  25. Y. Iwashima A. Abiko F. Ushikubi A. Hata K. Kaku H. Sano M. Eto (2001) ArticleTitleDownregulation of the voltage-dependent calcium channel (VDCC) β-subunit mRNAs in pancreatic islets of type 2 diabetic rats Biochem. Biophys. Res. Commun. 280 923–932 Occurrence Handle10.1006/bbrc.2000.4122 Occurrence Handle1:CAS:528:DC%2BD3MXls1agtw%3D%3D Occurrence Handle11162613

    Article  CAS  PubMed  Google Scholar 

  26. Y. Iwashima W. Pugh A.M. Depaoli J. Takeda S. Seino G.I. Bell K.S. Polonsky (1993) ArticleTitleExpression of calcium channel mRNAs in rat pancreatic islets and downregulation after glucose infusion Diabetes 42 948–955 Occurrence Handle1:CAS:528:DyaK3sXlsFOnsbg%3D Occurrence Handle7685720

    CAS  PubMed  Google Scholar 

  27. J. Ji S.N. Yang X. Huang X. Li L. Sheu N. Diamant P.O. Berggren H.Y. Gaisano (2002) ArticleTitleModulation of L-type Ca2+ channels by distinct domains within SNAP-25 Diabetes 51 1425–1436 Occurrence Handle1:CAS:528:DC%2BD38XjtlGmt7c%3D Occurrence Handle11978639

    CAS  PubMed  Google Scholar 

  28. H. Jijakli W.J. Malaisse (1998) ArticleTitleVerapamil- and cadmium-resistant stimulation of calcium uptake and insulin release by D-glucose in depolarised pancreatic islets exposed to diazoxide Cell Signal. 10 661–665 Occurrence Handle10.1016/S0898-6568(98)00009-6 Occurrence Handle1:CAS:528:DyaK1cXmtFKqtL0%3D Occurrence Handle9794248

    Article  CAS  PubMed  Google Scholar 

  29. G. Kang G.G. Holz (2003) ArticleTitleAmplification of exocytosis by Ca2+-induced Ca2+ release in INS-1 pancreatic β-cells J. Physiol. 546 175–189 Occurrence Handle1:CAS:528:DC%2BD3sXhsFWgtLo%3D

    CAS  Google Scholar 

  30. Y. Kang X. Huang E.A. Pasyk J. Ji G.G. Holz M.B. Wheeler R.G. Tsushima H.Y. Gaisano (2002) ArticleTitleSyntaxin-3 and syntaxin-1A inhibit L-type calcium channel activity, insulin biosynthesis and exocytosis in β-cell lines Diabetologia 45 231–241 Occurrence Handle10.1007/s00125-001-0718-0 Occurrence Handle1:CAS:528:DC%2BD38Xhs1enu7g%3D Occurrence Handle11935155

    Article  CAS  PubMed  Google Scholar 

  31. T. Kanno P. Rorsman S.O. Gopel (2002) ArticleTitleGlucose-dependent regulation of rhythmic action potential firing in pancreatic beta-cells by KATP-channel modulation J. Physiol. 545 501–507 Occurrence Handle10.1113/jphysiol.2002.031344 Occurrence Handle1:CAS:528:DC%2BD3sXktFyisw%3D%3D Occurrence Handle12456829

    Article  CAS  PubMed  Google Scholar 

  32. M. Kohler S. Norgren P.O. Berggren B.B. Fredholm O. Larsson C.J. Rhodes T.P. Herbert H. Luthman (1998) ArticleTitleChanges in cytoplasmic ATP concentration parallel changes in ATP-regulated K+-channel activity in insulin-secreting cells FEBS Lett. 441 97–102 Occurrence Handle10.1016/S0014-5793(98)01539-7 Occurrence Handle1:CAS:528:DyaK1cXotVKjsL0%3D Occurrence Handle9877173

    Article  CAS  PubMed  Google Scholar 

  33. C.A. Leech J.F. Habener (1997) ArticleTitleInsulinotropic glucagon-like peptide-1-mediated activation of non-selective cation currents in insulinoma cells is mimicked by maitotoxin J. Biol. Chem. 272 17987–17993 Occurrence Handle10.1074/jbc.272.29.17987 Occurrence Handle1:CAS:528:DyaK2sXkslKnsbs%3D Occurrence Handle9218425

    Article  CAS  PubMed  Google Scholar 

  34. C.A. Leech J.F. Habener (1998) ArticleTitleA role for Ca2+-sensitive nonselective cation channels in regulating the membrane potential of pancreatic β-cells Diabetes 47 1066–1073 Occurrence Handle1:CAS:528:DyaK1cXkt1ajurw%3D Occurrence Handle9648830

    CAS  PubMed  Google Scholar 

  35. B. Ligon A.E. Boyd K. Dunlap (1998) ArticleTitleClass A calcium channel variants in pancreatic islets and their role in insulin secretion J. Biol. Chem. 273 13905–13911 Occurrence Handle10.1074/jbc.273.22.13905 Occurrence Handle1:CAS:528:DyaK1cXjvVeisr8%3D Occurrence Handle9593738

    Article  CAS  PubMed  Google Scholar 

  36. G. Liu N. Dilmac N. Hilliard G.H. Hockerman (2003) ArticleTitleCav1.3 is preferentially coupled to glucose-stimulated insulin secretion in the pancreatic β-cell line INS-1 J. Pharmacol. Exp. Ther. 305 271–278 Occurrence Handle10.1124/jpet.102.046334 Occurrence Handle1:CAS:528:DC%2BD3sXis1anu7s%3D Occurrence Handle12649379

    Article  CAS  PubMed  Google Scholar 

  37. Y. Liu E. Gylfe (1997) ArticleTitleStore-operated Ca2+ entry in insulin-releasing pancreatic β-cells Cell Calcium 22 277–286 Occurrence Handle10.1016/S0143-4160(97)90066-X Occurrence Handle1:CAS:528:DyaK2sXnsVehurw%3D Occurrence Handle9481478

    Article  CAS  PubMed  Google Scholar 

  38. P.E. MacDonald S. Sewing J. Wang J.W. Joseph S.R. Smukler G. Sakellaropoulos M.C. Saleh C.B. Chan R.G. Tsushima A.M. Salapatek M.B. Wheeler (2002) ArticleTitleInhibition of KV2.1 voltage-dependent K+ channels in pancreatic β-cells enhances glucose-dependent insulin secretion J. Biol. Chem. 277 44938–44945 Occurrence Handle10.1074/jbc.M205532200 Occurrence Handle1:CAS:528:DC%2BD38Xosl2mt70%3D Occurrence Handle12270920

    Article  CAS  PubMed  Google Scholar 

  39. V. Magnelli A. Avaltroni E. Carbone (1996) ArticleTitleA single non-L-, non-N-type Ca2+ channel in rat insulin-secreting RINm5F cells Pfluegers Arch. 431 341–452 Occurrence Handle1:CAS:528:DyaK28XjtFagtLg%3D

    CAS  Google Scholar 

  40. C. Marchetti C. Amico D. Podesta M. Robello (1994) ArticleTitleInactivation of voltage-dependent calcium current in an insulinoma cell line Eur. Biophys. J. 23 51–58 Occurrence Handle10.1007/BF00192205 Occurrence Handle1:CAS:528:DyaK2cXltlSrtr0%3D Occurrence Handle8206006

    Article  CAS  PubMed  Google Scholar 

  41. Y. Matsuda H. Saegusa S. Zong T. Noda T. Tanabe (2001) ArticleTitleMice lacking Cav2.3 (α1E ) calcium channel exhibit hyperglycemia Biochem. Biophys. Res. Commun. 289 791–795 Occurrence Handle10.1006/bbrc.2001.6051 Occurrence Handle1:CAS:528:DC%2BD3MXovVWitb0%3D Occurrence Handle11735114

    Article  CAS  PubMed  Google Scholar 

  42. D. Mears I. Atwater (2000) Electrophysiology of the pancreatic β-cell . LeRoith S.I. Taylor J.M. Olefsky (Eds) Diabetes Mellitus—A Fundamental and Clinical Text EditionNumber2 Lippincott, Williams & Wilkins Philadelphia 47–60

    Google Scholar 

  43. D. Mears C.L. Zimliki (2004) ArticleTitleMuscarinic agonists activate Ca2+ store-operated and -independent ionic currents in insulin-secreting HIT-T15 cells and mouse pancreatic β-cells J. Membrane Biol. 197 59–70 Occurrence Handle10.1007/s00232-003-0642-y Occurrence Handle1:CAS:528:DC%2BD2cXhvF2mt7k%3D

    Article  CAS  Google Scholar 

  44. HP. Meissner H. Schmelz (1974) ArticleTitleMembrane potential of β-cells in pancreatic islets Pfluegers Arch. 351 195–206 Occurrence Handle10.1007/BF00586918 Occurrence Handle1:CAS:528:DyaE2cXlsV2ntrg%3D

    Article  CAS  Google Scholar 

  45. S. Misler D.W. Barnett K.D. Gillis D.M. Pressel (1992) ArticleTitleElectrophysiology of stimulus-secretion coupling in human β-cells Diabetes 41 1221–1228 Occurrence Handle1:CAS:528:DyaK38XmtVGmt7w%3D Occurrence Handle1397696

    CAS  PubMed  Google Scholar 

  46. Y. Miura J. Henquin P. Gilon (1997) ArticleTitleEmptying of intracellular Ca2+ stores stimulates Ca2+ entry in mouse pancreatic β-cells by both direct and indirect mechanisms J. Physiol. 503 387–398 Occurrence Handle10.1111/j.1469-7793.1997.387bh.x Occurrence Handle1:CAS:528:DyaK2sXmt1ylurY%3D Occurrence Handle9306280

    Article  CAS  PubMed  Google Scholar 

  47. Y. Namkung N. Skrypnyk M.J. Jeong T. Lee M.S. Lee H.L. Kim H. Chin P.G. Suh S.S. Kim H.S. Shin (2001) ArticleTitleRequirement for the L-type Ca2+ channel α1D subunit in postnatal pancreatic β-cell generation J. Clin. Invest. 108 1015–1022 Occurrence Handle10.1172/JCI200113310 Occurrence Handle1:CAS:528:DC%2BD3MXnt1Crsro%3D Occurrence Handle11581302

    Article  CAS  PubMed  Google Scholar 

  48. A.B. Parekh R. Penner (1997) ArticleTitleStore depletion and calcium influx Physiol. Rev. 77 901–930 Occurrence Handle1:CAS:528:DyaK2sXnt1yhtr0%3D Occurrence Handle9354808

    CAS  PubMed  Google Scholar 

  49. A. Pereverzev M. Mikhna R. Vajna C. Gissel M. Henry M. Weiergraber J. Hescheler N. Smyth T. Schneider (2002) ArticleTitleDisturbances in glucose-tolerance, insulin-release, and stress-induced hyperglycemia upon disruption of the Cav2.3 (α1E ) subunit of voltage-gated Ca2+ channels Mol. Endocrinol. 16 884–895 Occurrence Handle10.1210/me.16.4.884 Occurrence Handle1:CAS:528:DC%2BD38XivVehu7k%3D Occurrence Handle11923483

    Article  CAS  PubMed  Google Scholar 

  50. E. Perez-Reyes X.Y. Wei A. Castellano L. Birnbaumer (1990) ArticleTitleMolecular diversity of L-type calcium channels. Evidence for alternative splicing of the transcripts of three non-allelic genes J. Biol. Chem. 265 20430–20436 Occurrence Handle1:CAS:528:DyaK3cXlvVGqsbc%3D Occurrence Handle2173707

    CAS  PubMed  Google Scholar 

  51. T.D. Plant (1988) ArticleTitleProperties and calcium-dependent inactivation of calcium currents in cultured mouse pancreatic β-cells J. Physiol. 404 731–747 Occurrence Handle1:STN:280:BiaA3M7hs1Q%3D Occurrence Handle2855352

    CAS  PubMed  Google Scholar 

  52. J. Platzer J. Engel A. Schrott-Fischer K. Stephan S. Bova H. Chen H. Zheng J. Striessnig (2000) ArticleTitleCongenital deafness and sinoatrial node dysfunction in mice lacking class D L-type Ca2+ channels Cell 102 89–97 Occurrence Handle10.1016/S0092-8674(00)00013-1 Occurrence Handle1:CAS:528:DC%2BD3cXkvFCrtro%3D Occurrence Handle10929716

    Article  CAS  PubMed  Google Scholar 

  53. A. Pollo M. Lovallo E. Biancardi E. Sher C. Socci E. Carbone (1993) ArticleTitleSensitivity to dihydropyridines, omega-conotoxin and noradrenaline reveals multiple high-voltage-activated Ca2+ channels in rat insulinoma and human pancreatic β-cells Pfluegers Arch. 423 462–471 Occurrence Handle10.1007/BF00374942 Occurrence Handle1:CAS:528:DyaK3sXltlKgt7s%3D

    Article  CAS  Google Scholar 

  54. F. Qian P. Huang L. Ma A. Kuznetsov N. Tamarina L.H. Philipson (2002) ArticleTitleTRP genes: Candidates for nonselective cation channels and store-operated channels in insulin-secreting cells Diabetes 51 S183–189 Occurrence Handle1:CAS:528:DC%2BD38XhtVaqsbw%3D Occurrence Handle11815479

    CAS  PubMed  Google Scholar 

  55. M.W. Roe J.F. Worley F. Qian N. Tamarina A.A. Mittal F. Dralyuk N.T. Blair R.J. Mertz L.H. Philipson I.D. Dukes (1998) ArticleTitleCharacterization of a Ca2+ release-activated nonselective cation current regulating membrane potential and [Ca2+]i oscillations in transgenically derived β-cells J. Biol. Chem. 273 10402–10410 Occurrence Handle10.1074/jbc.273.17.10402 Occurrence Handle1:CAS:528:DyaK1cXivFKntLo%3D Occurrence Handle9553098

    Article  CAS  PubMed  Google Scholar 

  56. E. Rojas J. Hidalgo P.B. Carroll M.X. Li I. Atwater (1990) ArticleTitleA new class of calcium channels activated by glucose in human pancreatic β-cells FEBS Lett. 261 265–270 Occurrence Handle10.1016/0014-5793(90)80568-4 Occurrence Handle1:CAS:528:DyaK3cXitFCgur0%3D Occurrence Handle2155821

    Article  CAS  PubMed  Google Scholar 

  57. H. Safayhi H. Haase U. Kramer A. Bihlmayer M. Roenfeldt H.P. Ammon M. Froschmayr T.N. Cassidy I. Morano M.K. Ahlijanian J. Striessnig (1997) ArticleTitleL-type calcium channels in insulin-secreting cells: biochemical characterization and phosphorylation in RINm5F cells Mol. Endocrinol. 11 619–629 Occurrence Handle10.1210/me.11.5.619 Occurrence Handle1:CAS:528:DyaK2sXjtVyqtb8%3D Occurrence Handle9139805

    Article  CAS  PubMed  Google Scholar 

  58. H. Sakura F.M. Ashcroft (1997) ArticleTitleIdentification of four trp1 gene variants in murine pancreatic β-cells Diabetologia 40 528–532 Occurrence Handle10.1007/s001250050711 Occurrence Handle1:CAS:528:DyaK2sXjtVOrsbo%3D Occurrence Handle9165220

    Article  CAS  PubMed  Google Scholar 

  59. R.M. Santos L.M. Rosario A. Nadal J. Garcia-Sancho B. Soria M. Valdeolmillos (1991) ArticleTitleWidespread synchronous [Ca2+]i oscillations due to bursting electrical activity in single pancreatic islets Pfluegers Arch. 418 417–422 Occurrence Handle10.1007/BF00550880 Occurrence Handle1:STN:280:By6A2czjvF0%3D

    Article  CAS  Google Scholar 

  60. L.S. Satin (2000) ArticleTitleLocalized Ca2+ influx in pancreatic β-cells: its significance for Ca2+-dependent insulin secretion from the islets of Langerhans Endocrine 13 251–262 Occurrence Handle10.1385/ENDO:13:3:251 Occurrence Handle1:CAS:528:DC%2BD3MXovVeitA%3D%3D Occurrence Handle11216635

    Article  CAS  PubMed  Google Scholar 

  61. L.S. Satin D.L. Cook (1989) ArticleTitleCalcium current inactivation in insulin-secreting cells is mediated by calcium influx and membrane depolarization Pfluegers Arch. 414 1–10 Occurrence Handle10.1007/BF00585619 Occurrence Handle1:STN:280:BiaB28zmslY%3D

    Article  CAS  Google Scholar 

  62. L.S. Satin S.J. Tavalin T.A. Kinard J. Teague (1995) ArticleTitleContribution of L- and non-L-type calcium channels to voltage-gated calcium current and glucose-dependent insulin secretion in HIT-T15 cells Endocrinology 136 4589–4601 Occurrence Handle10.1210/en.136.10.4589 Occurrence Handle1:CAS:528:DyaK2MXot1WlsLs%3D Occurrence Handle7545106

    Article  CAS  PubMed  Google Scholar 

  63. A. Schmidt J. Hescheler S. Offermanns K. Spicher K.D. Hinsch F.J. Klinz J. Codina L. Birnbaumer H. Gausepohl R. Frank et al. (1991) ArticleTitleInvolvement of pertussis toxin-sensitive G-proteins in the hormonal inhibition of dihydropyridine-sensitive Ca2+ currents in an insulin-secreting cell line (RINm5F) J. Biol. Chem. 266 18025–18033 Occurrence Handle1:CAS:528:DyaK3MXlvF2nt7g%3D Occurrence Handle1680855

    CAS  PubMed  Google Scholar 

  64. V. Schulla E. Renstrom R. Feil S. Feil I. Franklin A. Gjinovci X.J. Jing D. Laux I. Lundquist M.A. Magnuson S. Obermuller C.S. Olofsson A. Salehi A. Wendt N. Klugbauer C.B. Wollheim P. Rorsman F. Hofmann (2003) ArticleTitleImpaired insulin secretion and glucose tolerance in beta cell-selective Cav1.2 Ca2+ channel null mice EMBO J. 22 3844–3854 Occurrence Handle10.1093/emboj/cdg389 Occurrence Handle1:CAS:528:DC%2BD3sXlsl2ksLk%3D Occurrence Handle12881419

    Article  CAS  PubMed  Google Scholar 

  65. S. Seino L. Chen M. Seino O. Blondel J. Takeda J.H. Johnson G.I. Bell (1992) ArticleTitleCloning of the α1 subunit of a voltage-dependent calcium channel expressed in pancreatic β-cells Proc. Natl. Acad. Sci. USA 89 584–588 Occurrence Handle1:CAS:528:DyaK3sXhvVGqu7s%3D Occurrence Handle1309948

    CAS  PubMed  Google Scholar 

  66. Z.H. Sheng R.E. Westenbroek W.A. Catterall (1998) ArticleTitlePhysical link and functional coupling of presynaptic calcium channels and the synaptic vesicle docking/fusion machinery J. Bioenerg. Biomembr. 30 335–345 Occurrence Handle10.1023/A:1021985521748 Occurrence Handle1:CAS:528:DyaK1cXmtlyrtL4%3D Occurrence Handle9758330

    Article  CAS  PubMed  Google Scholar 

  67. E. Sher E. Biancardi A. Polio E. Carbone G. Li C.B. Wollheim F. Clementi (1992) ArticleTitleω-Conotoxin-sensitive, voltage-operated Ca2+ channels in insulin-secreting cells Eur. J. Pharmacol. 216 407–414 Occurrence Handle10.1016/0014-2999(92)90438-A Occurrence Handle1:CAS:528:DyaK38XkvVert78%3D Occurrence Handle1330583

    Article  CAS  PubMed  Google Scholar 

  68. R. Vajna U. Klockner A. Pereverzev M. Weiergraber X. Chen G. Miljanich N. Klugbauer J. Hescheler E. Perez-Reyes T. Schneider (2001) ArticleTitleFunctional coupling between ’R-type’ Ca2+ channels and insulin secretion in the insulinoma cell line INS-1 Eur. J. Biochem. 268 1066–1075 Occurrence Handle10.1046/j.1432-1327.2001.01969.x Occurrence Handle1:CAS:528:DC%2BD3MXhsF2qu7c%3D Occurrence Handle11179973

    Article  CAS  PubMed  Google Scholar 

  69. R. Vajna M. Schramm A. Pereverzev S. Arnhold H. Grabsch U. Klockner E. Perez-Reyes J. Hescheler T. Schneider (1998) ArticleTitleNew isoform of the neuronal Ca2+ channel α1E subunit in islets of Langerhans and kidney—distribution of voltage-gated Ca2+ channel α1 subunits in cell lines and tissues Eur. J. Biochem. 257 274–285 Occurrence Handle10.1046/j.1432-1327.1998.2570274.x Occurrence Handle1:CAS:528:DyaK1cXmsVyksLs%3D Occurrence Handle9799129

    Article  CAS  PubMed  Google Scholar 

  70. O. Wiser M.K. Bennett D. Atlas (1996) ArticleTitleFunctional interaction of syntaxin and SNAP-25 with voltage-sensitive L- and N-type Ca2+ channels EMBO J. 15 4100–4110 Occurrence Handle1:CAS:528:DyaK28Xmt1KktLw%3D Occurrence Handle8861939

    CAS  PubMed  Google Scholar 

  71. O. Wiser M. Trus A. Hernandez E. Renstrom S. Barg P. Rorsman D. Atlas (1999) ArticleTitleThe voltage sensitive LC-type Ca2+ channel is functionally coupled to the exocytotic machinery Proc. Natl. Acad. Sci. USA 96 248–253 Occurrence Handle10.1073/pnas.96.1.248 Occurrence Handle1:CAS:528:DyaK1MXjvV2gsA%3D%3D Occurrence Handle9874804

    Article  CAS  PubMed  Google Scholar 

  72. J.F. Worley Suffix3rd M.S. Mclntyre B. Spencer R.J. Mertz M.W. Roe I.D. Dukes (1994) ArticleTitleEndoplasmic reticulum calcium store regulates membrane potential in mouse islet β-cells J. Biol. Chem. 269 14359–14362 Occurrence Handle1:CAS:528:DyaK2cXjt1Shsb8%3D Occurrence Handle8182038

    CAS  PubMed  Google Scholar 

  73. S.N. Yang O. Larsson R. Branstrom A.M. Bertorello B. Leibiger I.B. Leibiger T. Moede M. Kohler B. Meister P.O. Berggren (1999) ArticleTitleSyntaxin 1 interacts with the LD subtype of voltage-gated Ca2+ channels in pancreatic β-cells Proc. Natl. Acad. Sci. USA 96 10164–10169 Occurrence Handle10.1073/pnas.96.18.10164 Occurrence Handle1:CAS:528:DyaK1MXlvFegtLk%3D Occurrence Handle10468580

    Article  CAS  PubMed  Google Scholar 

  74. H. Zhuang A. Bhattacharjee F. Hu M. Zhang T. Goswami L. Wang S. Wu P.O. Berggren M. Li (2000) ArticleTitleCloning of a T-type Ca2+ channel isoform in insulin-secreting cells Diabetes 49 59–64 Occurrence Handle1:CAS:528:DC%2BD3cXkt1yhtA%3D%3D Occurrence Handle10615950

    CAS  PubMed  Google Scholar 

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Acknowledgments

I thank Charles Zimliki for many helpful discussions and comments on this manuscript. Work in my laboratory is supported by the American Diabetes Association.

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Correspondence to David Mears.

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Mears, D. Regulation of Insulin Secretion in Islets of Langerhans by Ca2+Channels. J Membrane Biol 200, 57–66 (2004). https://doi.org/10.1007/s00232-004-0692-9

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