Pflügers Archiv

, Volume 422, Issue 5, pp 443–448 | Cite as

Demonstration of a novel apamin-insensitive calcium-activated K+ channel in mouse pancreatic B cells

  • Carina Ämmälä
  • Krister Bokvist
  • Olof Larsson
  • Per -Olof Berggren
  • Patrik Rorsman
Transport Processes, Metabolism and Endocrinology; Kidney, Gastrointestinal Tract, and Exocrine Glands


The whole-cell configuration of the patchclamp technique was used to characterize the biophysical and pharmacological properties of an oscillating K+-current that can be induced by intracellular application of GTP[γS] in mouse pancreatic B cells (Ämmälä et al. 1991). These K+ conductance changes are evoked by periodic increases in the cytoplasmic Ca2+ concentration ([Ca2+]i) and transiently repolarize the B cell, thus inhibiting action-potential firing and giving rise to a bursting pattern. GTP[γS]-evoked oscillations in K+ conductance were reversibly suppressed by a high (300 μM) concentration of carbamylcholine. By contrast, α2-adrenoreceptor stimulation by 20 μM clonidine did not interfere with the oscillatory behaviour but evoked a small sustained outward current. At 0 mV membrane potential, the oscillating K+-current elicited by GTP[γS] was highly sensitive to extracellular tetraethylammonium (TEA; 70% block by 1 mM). The TEA-resistant component, which carried approximately 80% of the current at −40 mV, was affected neither by apamin (1 μM) nor by tolbutamide (500 μM). The current evoked by internal GTP[γS] was highly selective for K+, as demonstrated by a 51-mV change in the reversal potential for a sevenfold change in [K+]o. Stationary fluctuation analysis indicated a unitary conductance of 0.5 pS when measured with symmetric (≈ 140mM) KCl solutions. The estimated singlechannel conductance with physiological ionic gradients is 0.1 pS. The results indicate the existence of a novel Ca2+-gated K+ conductance in pancreatic B cells. Activation of this K+ current may contribute to the generation of the oscillatory electrical activity characterizing the B cell at intermediate glucose concentrations.

Key words

K+-channel Ca2+ Apamin Pancreas Insulin 


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  1. 1.
    Ämmälä C, Larsson O, Berggren PO, Bokvist K, Juntti-Berggren L, Kindmark H, Rorsman P (1991) Inositol trisphosphate-dependent periodic activation of a Ca2+-activated K+-conductance in glucose-stimulated pancreatic β-cells. Nature 353:849–852Google Scholar
  2. 2.
    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 262:5448–5454Google Scholar
  3. 3.
    Ashcroft FM, Rorsman P (1989) Electrophysiology of the pancreatic B-cell. Prog Biophys Mol Biol 54:97–143Google Scholar
  4. 4.
    Blatz AL, Magleby KL (1986) Single apamin-blocked Ca2+-activated K+-channels of small conductance in rat cultured skeletal muscle. Nature 323:718–720Google Scholar
  5. 5.
    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) 423:311–325Google Scholar
  6. 6.
    Bokvist K, Rorsman P, Smith PA (1990) Block of ATP-regulated and Ca2+-activated K+-channels in mouse pancreatic β-cells by external tetraethylammonium and quinine. J Physiol (Lond) 423:327–342Google Scholar
  7. 7.
    Cook DL (1992) Electrical bursting in islet β cells. Nature 357:28Google Scholar
  8. 8.
    Cook DL, Ikeuchi M, Fujimoto WY (1984) Lowering of pHi inhibits Ca2+-activated K+-channels in pancreatic β-cells. Nature 311:269–271Google Scholar
  9. 9.
    Dunne MJ, Petersen OH (1991) Potassium selective ion channels in insulin-secreting cells: physiology, pharmacology and their role in stimulus-secretion coupling. Biochim Biophys Acta 1071:67–82Google Scholar
  10. 10.
    Fatherazi S, Cook DL (1991) Specificity of tetraethylammonium and quinine for three K channels in insulin-secreting cells. J Membr Biol 120:105–114Google Scholar
  11. 11.
    Grynkiewicz G, Poenie M, Tsien RY (1985) A new generation of Ca2+-indicators with greatly improved fluorescence properties. J Biol Chem 260:3440–3450Google Scholar
  12. 12.
    Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ (1981) Improved patch-clamp techniques for high resolution recording from cells and cell-free membrane patches. Pflügers Arch 391:85–100Google Scholar
  13. 13.
    Henquin JC (1990) Glucose-induced electrical activity in β-cells. Feedback control of ATP-sensitive K+-channels by Ca2+. Diabetes 39:1457–1460Google Scholar
  14. 14.
    Henquin JC, Meissner HP (1984) Significance of ionic fluxes and changes in membrane potential for stimulus secretion in pancreatic β-cells. Experientia 40:1043–1052Google Scholar
  15. 15.
    Kukuljan M, Gonçalves AA, Atwater I (1991) Charybdotoxin-sensitive KCa-channel is not involved in glucose-induced electrical activity in pancreatic β-cells. J Membr Biol 119:187–195Google Scholar
  16. 16.
    Lebrun P, Atwater I, Claret M, Malaisse WJ, Herchuelz A (1983) Resistance to apamin of the Ca2+-activated K+ permeability in pancreatic β-cells. FEBS Lett 161:41–44Google Scholar
  17. 17.
    Lund PE, Grapengiesser E, Gylfe E, Hellman B (1988) Intracellular ATP mimics GTPγS in generating Ca2+-oscillations in pancreatic β-cells. Biochim Biophys Res Commun 177:777–783Google Scholar
  18. 18.
    Penner R, Neher E (1988) The role of calcium in stimulus-secretion coupling in excitable and non-excitable cells. J Exp Biol 139:329–345Google Scholar
  19. 19.
    Rorsman P, Berggren PO (1992) Electrical bursting in islet β cells. Nature 357:28Google Scholar
  20. 20.
    Rorsman P, Trube G (1986) Calcium and delayed potassium currents in mouse β-cells under voltage-clamp conditions. J Physiol (Lond) 374:531–550Google Scholar
  21. 21.
    Rorsman P, Bokvist K, Ämmälä C, Arkhammar P, Berggren PO, Larsson O, Wåhlander K (1991) Activation by adrenaline of a lowconductance G protein-dependent K+ channel in mouse pancreatic B-cells. Nature 349:77–79Google Scholar
  22. 22.
    Rorsman P, Ämmälä C, Berggren PO, Bokvist K, Larsson O (1992) Cytoplasmic calcium transients due to single action potentials and voltage-clamp depolarizations in mouse pancreatic B-cells. EMBO J 11:2877–2884Google Scholar
  23. 23.
    Trube G, Rorsman P, Ohno-Shosaku T (1986) Opposite effects of tolbutamide and diazoxide on the ATP-dependent K+-channel in pancreatic β-cells. Pflügers Arch 407:493–499Google Scholar
  24. 24.
    Tse A, Hille B (1992) GnRH-induced Ca2+ oscillations and rhythmic hyperpolarizations of pituitary gonadotropes. Science 255:462–464Google Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • Carina Ämmälä
    • 1
  • Krister Bokvist
    • 1
  • Olof Larsson
    • 1
  • Per -Olof Berggren
    • 1
  • Patrik Rorsman
    • 1
  1. 1.Department of Medical BiophysicsGöteborgs UniversitetGöteborgSweden

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