Abstract
In glucose-stimulated pancreatic β-cells, the membrane potential alternates between a hyperpolarized silent phase and a depolarized phase with Ca2+ action potentials. The molecular and ionic mechanisms underlying these bursts of electrical activity remain unknown. We have observed that 10.2–12.8 mM Ca2+, 1 μM Bay K 8644 and 2 mM tetraethylammonium (TEA) trigger bursts of electrical activity and oscillations of intracellular free Ca2+ concentration ([Ca2+]i) in the presence of 100 μM tolbutamide. The [Ca2+]i was monitored from single islets of Langerhans using fura-2 microfluorescence techniques. Both the high-Ca2+ and Bay-K-8644 evoked [Ca2+]i oscillations overshot the [Ca2+]i recorded in tolbutamide. Nifedipine (10–20 μM) caused an immediate membrane hyperpolarization, which was followed by a slow depolarization to a level close to the burst active phase potential. The latter depolarization was accompanied by suppression of spiking activity. Exposure to high Ca2+ in the presence of nifedipine caused a steady depolarization of approximately 8 mV. Ionomycin (10 μM) caused membrane hyperpolarization in the presence of 7.7 mM Ca2+, which was not abolished by nifedipine. Charybdotoxin (CTX, 40–80 nM), TEA (2 mM) and quinine (200 μM) did not suppress the high-Ca2+-evoked bursts. It is concluded that: (1) the channel underlying the burst is sensitive to [Ca2+]i rises mediated by Ca2+ influx through L-type Ca2+ channels, (2) both the ATP-dependent K+ channel and the CTX and TEA-sensitive Ca2+-dependent K+ channel are highly unlikely to provide the pacemaker current underlying the burst. We propose that the burst is mediated by a distinct Ca2+-dependent K+ channel and/or by [Ca2+]idependent slow processes of inactivation of Ca2+ currents.
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References
Ammala C, Larsson O, Berggren P-O, 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: 849–852
Ashcroft FM, Rorsman P (1989) Electrophysiology of the pancreatic β-cell. Prog Biophys Mol Biol 54: 87–143
Atwater I, Dawson CM, Ribalet B, Rojas E (1979) Potassium permeability activated by intracellular calcium ion concentration in the pancreatic β-cell. J Physiol (Lond) 288: 575–588
Atwater I, Dawson CM, Eddlestone GT, Rojas E (1981) Voltage noise measurements across the pancreatic β-cell membrane: calcium channel characteristics. J Physiol (Lond) 314: 195–212
Atwater I, Rosario L, Rojas E (1983) Properties of the Caactivated K+ channel in pancreatic β-cells. Cell Calcium 4: 451–461
Atwater I, Carroll P, Li MX (1989) Electrophysiology of the pancreatic β-cell. In: Insulin secretion. Liss, New York, pp 49–68
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
Bokvist K, Rorsman P, Smith PA (1990) Block of ATP-regulated and Ca2+-activated K+ channels in mouse pancreatic βcells by external tetraethylammonium and quinine. J Physiol (Lond) 423: 327–342
Chad JE, Eckert R (1986) An enzymatic mechanism for calcium current inactivation in dialysed Helix neurones. J Physiol (Lond) 378: 31–51
Chay TR (1987) The effect of inactivation of calcium channels by intracellular Ca2+ ions in the bursting pancreatic β-cells. Cell Biophys 11: 77–90
Chay TR, Cook DL (1988) Endogenous bursting patterns in excitable cells. Math Biosci 90: 139–153
Chay TR, Keizer J (1983) Minimal model for membrane oscillations in the pancreatic β-cell. Biophys J 42: 181–190
Ferrer R, Atwater I, Omer EM, Gonçalves AA, Croghan PC, Rojas E (1984) Electrophysiological evidence for the inhibition of potassium permeability in pancreatic β-cells by glib enclamide. Q J Exp Physiol 69: 831–839
Grynkiewicz G, Poenie M, Tsien RY (1985) A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 260: 3440–3450
Henquin J-C (1988) ATP-sensitive K+ channels may control glucose-induced electrical activity in pancreatic β-cells. Biochem Biophys Res Commun 156: 769–775
Henquin J-C (1990) Glucose-induced electrical activity in β cells: feedback control of ATP-sensitive K+ channels by Ca2+. Diabetes 39: 1457–1460
Henquin J-C, Meissner HP (1984) Significance of ionic fluxes and changes in membrane potential for stimulus-secretion coupling in pancreatic β-cells. Experientia 40: 1043–1052
Henquin J-C, Schmeer W, Nenquin M, Meissner HP (1985) Effects of a calcium channel agonist on the electrical, ionic and secretory events in mouse pancreatic β-cells. Biochem Biophys Res Commun 131: 980–986
Keizer J, Smolen P (1991) Bursting electrical activity in pancreatic β-cells caused by Ca2+ and voltage-inactivated Ca2+ channels. Proc Natl Acad Sci USA 88: 3897–3901
Kramer RH, Zucker RS (1985) Calcium-induced inactivation of calcium current causes the inter-burst hyperpolarization of Aplysia bursting neurones. J Physiol (Lond) 362: 131–160
Kukuljan M, Gonçalves AA, Atwater I (1991) Charybdotoxin sensitive KCa channel is not involved in glucose-induced electrical activity in pancreatic β-cell. J Membr Biol 119: 187–195
Lebrun P, Atwater I (1985) Efects of the calcium channel agonist, Bay K 8644, on electrical activity in mouse pancreatic B-cells. Biophys J 48: 919–930
Mancilla E, Rojas E (1990) Quinine blocks the high conductance, calcium-activated potassium channel in rat pancreatic β-cells. FEBS Lett 260: 105–108
Meissner HP, Schmelz H (1974) Membrane potential of betacells in pancreatic islets. Pflügers Arch 351: 195–206
Nilsson T, Arkhammar P, Berggren P-O (1987) Extracellular Ca2+ induces a rapid increase in cytoplasmic free Ca2+ in pancreatic β-cells. Biochem Biophys Res Commun 149: 152–158
Petersen OH, Findlay I (1987) Electrophysiology of the pancreas. Physiol Rev 67: 1054–1116
Plant TD (1988) Properties and calcium-dependent inactivation of calcium currents in cultured mouse pancreatic β cells. J Physiol (Lond) 404: 731–747
Ribalet B, Beigelman PM (1980) Calcium action potentials and potassium permeability activation in pancreatic β-cells. Am J Physiol 239: C 124-C 133
Rinzel J (1985) Bursting oscillations in an excitable membrane model. In: Sleeman BD, Jarvis RJ (eds) Ordinary and partial differential equations. Springer, Berlin Heidelberg New York, pp 304–316
Rojas E, Hidalgo J, Carroll PB, Li MX, Atwater I (1990) A new class of calcium channels activated by glucose in human pancreatic β-cell. FEBS Lett 261: 265–270
Rorsman P, Ashcroft FM, Trube G (1988) Single Ca channel currents in mouse pancreatic B-cells. Pflügers Arch 412: 597–603
Rosario LM, Atwater I, Rojas E (1985) Membrane potential measurements in islets of Langerhans from ob/ob obese mice suggest an alteration in [Ca2+]i-activated K+ permeability. Q J Exp Physiol 70: 137–150
Rosario LM, Atwater I, Scott AM (1986) Pulsatile insulin release and electrical activity from single ob/ob mouse islets of Langerhans. Adv Exp Med Biol 211: 203–215
Santos RM, Rosario LM, Nadal A, Garcia-Sancho J, Soria B, Valdeolmillos M (1991) Widespread synchronous [Ca2+]i oscillations due to bursting electrical activity in single pancreatic islets. Pflügers Arch 418: 417–422
Santos RM, Barbosa RM, Silva AM, Antunes CM, Rosario LM (1992) High external Ca2+ levels trigger membrane potential oscillations in mouse pancreatic β-cells during blockade of K(ATP) channels. Biochem Biophys Res Commun 187: 872–879
Satin LS, Cook DL (1989) Calcium current inactivation in insulin-secreting cells is mediated by calcium influx and membrane depolarization. Pflügers Arch 414: 1–10
Satin LS, Hopkins WF, Fatherazi S, Cook DL (1989) Expression of a rapid, low-voltage threshold K current in insulinsecreting cells is dependent on intracellular calcium buffering. J Membr Biol 112: 213–222
Sherman A, Keizer J, Rinzel J (1990) Domain model for Ca2+ inactivation of Ca2+ channels at low channel density. Biophys J 58: 985–995
Valdeolmillos M, Santos RM, Contreras D, Soria B, Rosario LM (1989) Glucose-induced oscillations of intracellular Ca2+ concentration resembling bursting electrical activity in single mouse islets of Langerhans. FEBS Lett 259: 19–23
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Rosário, L.M., Barbosa, R.M., Antunes, C.M. et al. Bursting electrical activity in pancreatic β-cells: evidence that the channel underlying the burst is sensitive to Ca2+ influx through L-type Ca2+ channels. Pflügers Arch. 424, 439–447 (1993). https://doi.org/10.1007/BF00374906
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DOI: https://doi.org/10.1007/BF00374906