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Nucleotide regulation of a calcium-activated cation channel in the rat insulinoma cell line, CRI-G1

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Abstract

The nucleotide regulation of a calcium-activated nonselective cation (Ca-NS+) channel has been investigated in the rat insulinoma cell line CRI-G1. The activity of the channel is reduced by both AMP and ADP (1–100 μm) in a concentration-dependent manner, with AMP being more potent than ADP. At lower concentrations (0.1–5 μm), both ADP and AMP activate the channel in some patches. Examination of the nucleotide specificity of channel inhibition indicates a high selectivity for AMP over the other nucleotides tested with a rank order of potency of AMP > UMP > CMP ≥GMP. Cyclic nucleotides also modulate channel activity in a complex, concentration-dependent way. Cyclic AMP exhibits a dual effect, predominantly increasing channel activity at low concentrations (0.1–10 μm) and reducing it at higher concentrations (100 μm and 1 mm). Specificity studies indicate that the cyclic nucleotide site mediating inhibition of channel activity exhibits a strong preference for cyclic AMP over cyclic GMP, with cyclic UMP being almost equipotent with cyclic AMP. Cyclic IMP and cyclic CMP are not active at this site. The cyclic nucleotide site mediating activation of the channel shows much less nucleotide specificity than the inhibitory site, with cyclic AMP, cyclic GMP and cyclic IMP being almost equally active.

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References

  • Ashcroft, F.M. 1988. Adenosine 5′-triphosphate-sensitive potassium channels. Annu. Rev. Neurosci. 11:97–118

    Google Scholar 

  • Ashcroft, F.M., Rorsman, P. 1991. Electrophysiology of the pancreatic β-cell. Prog. Biophys. Mol. Biol. 54:87–143

    Google Scholar 

  • Bevan, S., Gray, P.T.A., Ritchie, J.M. 1984. A calcium-activated cation-selective channel in rat cultured Schwann cells. Proc. R. Soc. (Lond.) B. 222:349–355

    Google Scholar 

  • Bokvist, K., Ämmälä, C., Ashcroft, F.M., Berggren, P.-O., Larsson, O., Rorsman, P. 1991. Separate processes mediate nucleotide-induced inhibition and stimulation of the ATP-regulated K+-channels in mouse pancreatic β-cells. Proc. R. Soc. (Lond.) B. 243:139–144

    Google Scholar 

  • Burnstock, G. 1978. A basis of distinguishing two types of purinergic receptor. In: Cell Membrane Receptors for Drugs and Hormones: A Multidisciplinary Approach. L. Bolis and R.W. Straub, editors. pp. 107–118. Raven, New York

    Google Scholar 

  • Carrington, C.A., Rubery, E.D., Pearson, E.C., Hales, C.N. 1986. Five new insulin-producing cell lines with differing secretory properties. J. Endocrinol. 109:193–200

    Google Scholar 

  • Cheng, H.-C., Kemp, B.E., Pearson, R.B., Smith, A.J., Misconi, L., Van Patten, S.M., Walsh, D.A. 1986. A potent synthetic peptide inhibitor of the cAMP-dependent protein kinase. J. Biol. Chem. 261:989–992

    Google Scholar 

  • Colquhoun, D., Neher, E., Reuter, H., Stevens, C.F. 1981. Inward current channels activated by intracellular Ca2+ in cultured cardiac cells. Nature 294:752–754

    Google Scholar 

  • Cook, D.L., Hales, C.N. 1984. Intracellular ATP directly blocks K+ channels in pancreatic β-cells. Nature 311:271–273

    Google Scholar 

  • Cook, D.I., Poronnik, P., Young, J.A. 1990. Characterization of a 25pS nonselective cation channel in a cultured secretory epithelial cell line. J. Membrane Biol. 114:37–52

    Google Scholar 

  • Cook, D.L., Satin, L.S., Ashford, M.L.J., Hales, C.N. 1988. ATP-sensitive K+ channels in pancreatic β-cells. Spare-channel hypothesis. Diabetes 37:495–498

    Google Scholar 

  • Dempster, J. 1988. Computer analysis of electrophysiological signals. In: Microcomputers in Physiology: A Practical Approach. P.J. Fraser, editor. pp. 51–92. IRL, Oxford

    Google Scholar 

  • De Weille, J.R., Schmid-Antomarchi, H., Fosset, M., Lazdunski, M. 1989. Regulation of ATP-sensitive K+ channels in insulinoma cells: Activation by somatostatin and protein kinase C and the role of cAMP. Proc. Natl. Acad. Sci. USA 86:2971–2975

    Google Scholar 

  • Dhallan, R.S., Yau, K.-W., Schrader, K.A., Reed, R.R. 1990. Primary structure and functional expression of a cyclic nucleotide-activated channel from olfactory neurons. Nature 347:184–187

    Google Scholar 

  • DiFrancesco, D., Tortora, P. 1991. Direct activation of cardiac pacemaker channels by intracellular cyclic AMP. Nature 351:145–147

    Google Scholar 

  • Dunne, M.J., Gallacher, D.V., Petersen, O.H., Yule, D.I. 1989. Na+-dependent glucose-evoked depolarization and increase in [Ca2+]i in the rat insulinoma cell line RINm5F. J. Physiol. 415:93P

  • Dunne, M.J., Petersen, O.H. 1986a. GTP and GDP activation of K+ channels that can be inhibited by ATP. Pfluegers Arch. 407:564–565

    Google Scholar 

  • Dunne, M.J., Petersen, O.H. 1986b. Intracellular ADP activates K+ channels that are inhibited by ATP in an insulin-secreting cell line. FEBS Lett. 208:59–62

    Google Scholar 

  • Dunne, M.J., West-Jordan, J.A., Abraham, R.J., Edwards, R.H.T., Petersen, O.H. 1988. The gating of nucleotide-sensitive K+-channels in insulin-secreting cells can be modulated by changes in the ratio ATP4−/ADP3− and by nonhydrolyzable derivatives of both ATP and ADP. J. Membrane Biol. 104:165–177

    Google Scholar 

  • Dunne, M.J., Yule, D.I., Gallacher, D.V., Petersen, O.H. 1990. Stimulant-evoked depolarization and increase in [Ca2+] i in insulin-secreting cells is dependent on external Na+. J. Membrane Biol. 113: 131–138

    Google Scholar 

  • Fesenko, E., Kolesnikov, S., Lyubarsky, A. 1985. Induction by cyclic GMP of cationic conductance in plasma membrane of retinal rod outer segment. Nature 313:310–313

    Google Scholar 

  • Filatov, G.N., Jainazarov, A.B., Kolesnikov, S.S., Lyubarsky, A.L., Fesenko, E.E. 1989. The effect of ATP, GTP, and cAMP on the cGMP-dependent conductance of the fragments from frog rod plasma membrane. FEBS Lett. 245:185–188

    Google Scholar 

  • Furman, R.E., Tanaka, J.C. 1989. Photoreceptor channel activation: Interaction between cAMP and cGMP. Biochemistry 28:2785–2788

    Google Scholar 

  • Hamill, O.P., Marty, A., Neher, E., Sakmann, B., Sigworth, F.J. 1981. Improved patch-clamp techniques for high-resolution recording from cells and cell-free membrane patches. Pfluegers Arch. 391: 85–100

    Google Scholar 

  • Haynes, L., Yau, K. 1985. Cyclic GMP-sensitive conductance in outer segment membrane of catfish cones. Nature 317:61–64

    Google Scholar 

  • Hille, B. 1984. Ionic Channels of Excitable Membranes. Sinauer Associates, Sunderland, MA

    Google Scholar 

  • Hockberger, P.E., Swandulla, D. 1987. Direct ion channel gating: a new function for intracellular messengers. Cell. Mol. Neurobiol. 7:229–236

    Google Scholar 

  • Hopkins, W.F., Fatherazi, S., Peter-Riesch, B., Corkey, B.E., Cook, D.L. 1992. Two sites for adenine-nucleotide regulation of ATP-sensitive potassium channels in mouse pancreatic β-cells and HIT cells. J. Membrane Biol. 129:287–295

    Google Scholar 

  • Ildefonse, M., Crouzy, S., Bennett, N. 1992. Gating of retinal rod cation channel by different nucleotides: comparative study of unitary currents. J. Membrane Biol. 130:91–104

    Google Scholar 

  • Kakei, M., Noma, A., Shibasaki, T. 1985. Properties of adeninetriphosphate-regulated potassium channels in guinea pig ventricular cells. J. Physiol. 363:441–462

    Google Scholar 

  • Kass, R.S., Lederer, W.J., Tsien, R.W., Weingart, R. 1978. Role of calcium ions in transient inward currents and after contractions induced by strophantidin in cardiac Purkinje fibres. J. Physiol. 281: 187–208

    Google Scholar 

  • Kaupp, U.B. 1991. The cyclic nucleotide-gated channels of vertebrate photoreceptors and olfactory epithelium. Trends. Neurosci. 14: 150–157

    Google Scholar 

  • Kozlowski, R.Z., Ashford, M.L.J. 1990. ATP-sensitive K+-channel run-down is Mg2+ dependent. Proc. R. Soc. (Lond.) B. 240:397–410

    Google Scholar 

  • Kozlowski, R.Z., Hales, C.N., Ashford, M.L.J. 1989. Dual effects of diazoxide on ATP-K+-currents recorded from an insulin-secreting cell line. Br. J. Pharmacol. 97:1039–1050

    Google Scholar 

  • Lederer, W.J., Nichols, C.G. 1989. Nucleotide modulation of the activity of rat heart ATP-sensitive K+ channels in isolated membrane patches. J. Physiol. 419:193–211

    Google Scholar 

  • Maruyama, Y., Petersen, O.H. 1982. Cholecystokinin activation of single-channel currents is mediated by internal messenger in pancreatic acinar cells. Nature 299:159–161

    Google Scholar 

  • Maruyama, Y., Petersen, O.H. 1984. Single calcium-dependent cation channels in mouse pancreatic acinar cells. J. Membrane Biol. 81: 83–87

    Google Scholar 

  • Misler, S., Falke, L.C., Gillis, K., McDaniel, M.L. 1986. A metabolite-regulated potassium channel in rat pancreatic β-cells. Proc. Natl. Acad. Sci. USA 83:7119–7123

    Google Scholar 

  • Nakamura, T., Gold, G. 1987. A cyclic nucleotide-gated conductance in olfactory receptor cilia. Nature 325:442–444

    Google Scholar 

  • Partridge, L.D., Swandulla, D. 1988. Calcium-activated non-specific cation channels. Trends. Neurosci. 11:69–72

    Google Scholar 

  • Paulais, M., Teulon, J. 1989. A cation channel in the thick ascending limb of Henle's loop of the mouse kidney: inhibition by adenine nucleotides. J. Physiol. 413:315–327

    Google Scholar 

  • Prentki, M., Matschinsky, F.M. 1987. Ca2+, cAMP, and phospholipid-derived messengers in coupling mechanisms of insulin secretion. Physiol. Rev. 67:1185–1248

    Google Scholar 

  • Reale, V. 1992. Nucleotide Modulation of Non-Selective Cation Channels in an Insulin-secreting Cell Line. Ph.D. Thesis, University of Cambridge

  • Reale, V., Hales, C.N., Ashford, M.L.J. 1992. Cyclic AMP regulates a calcium-activated non-selective cation channel in a rat insulinoma cell line. J. Physiol. 446:312P

  • Spruce, A.E., Standen, N.B., Stanfield, P.R. 1985. Voltage-dependent ATP-sensitive potassium channels of skeletal muscle membrane. Nature 316:736–738

    Google Scholar 

  • Spruce, A.E., Standen, N.B., Stanfield, P.R. 1986. The effect of nucleotides on the adenosine triphosphate-regulated potassium channel in frog skeletal muscle. J. Physiol. 373:63P

  • Spruce, A.E., Standen, N.B., Stanfield, P.R. 1987. Studies of the unitary properties of adenosine-5′-triphosphate-regulated potassium channels of frog skeletal muscle. J. Physiol. 382:213–236

    Google Scholar 

  • Stoeckel, H., Takeda, K. 1989. Calcium-activated, voltage-dependent, non-selective cation currents in endosperm plasma membrane from higher plants. Proc. R. Soc. (Lond.) B. 237:213–231

    Google Scholar 

  • Sturgess, N.C., Ashford, M.L.J., Cook, D.L., Hales, C.N. 1986a. Single channel recordings of potassium currents in an insulin secreting cell line. J. Endocrinol. 109:201–207

    Google Scholar 

  • Sturgess, N.C., Hales, C.N., Ashford, M.L.J. 1986b. Inhibition of a calcium-activated non-selective cation channel, in a rat insulinoma cell line, by adenine derivatives. FEBS Lett. 208:397–400

    Google Scholar 

  • Sturgess, N.C., Hales, C.N., Ashford, M.L.J. 1987. Calcium and ATP regulate the activity of a non-selective cation channel in a rat insulinoma cell line. Pfluegers Arch. 409:607–615

    Google Scholar 

  • Swandulla, D., Partridge, L.D. 1990. Non-specific cation channels. In: Potassium Channels. Structure, Classification, Function and Therapeutical Potential. N.S. Cook, editor. pp. 167–180. Ellis Horwood, Chichester, UK

    Google Scholar 

  • Tanaka, J.C., Eccleston, J.F., Furman, R.E. 1989. Photoreceptor channel activation by nucleotide derivatives. Biochemistry 28:2776–2784

    Google Scholar 

  • Thorn, P., Petersen, O.H. 1992. Activation of nonselective cation channels by physiological cholecystokinin concentrations in mouse pancreatic acinar cells. J. Gen. Physiol. 100:11–25

    Google Scholar 

  • Tung, R.T., Kurachi, Y. 1991. On the mechanism of nucleotide diphosphate activation of the ATP-sensitive K+ channel in ventricular cell of guinea-pig. J. Physiol. 437:239–256

    Google Scholar 

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Author notes

  1. V. Reale

    Present address: AFRC Laboratory Molecular Signalling, Department of Zoology, University of Cambridge, Downing Street, CB2 3EJ, Cambridge, UK

Authors and Affiliations

  1. Department of Clinical Biochemistry, University of Cambridge, New Addenbrookes Hospital, Hills Road, CB2 2QD, Cambridge, UK

    V. Reale & C. N. Hales

  2. Department of Pharmacology, University of Cambridge, Tennis Court Road, CB2 1QJ, Cambridge, UK

    M. L. J. Ashford

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  1. V. Reale
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  2. C. N. Hales
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  3. M. L. J. Ashford
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Additional information

We thank Dr P.D. Evans for his comments on the manuscript, and the British Diabetic Association, Serono Diagnostic (UK) Ltd., and the Wolfson Trust for support. V.R. was supported by a grant from Serono Diagnostic (UK) Ltd.

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Reale, V., Hales, C.N. & Ashford, M.L.J. Nucleotide regulation of a calcium-activated cation channel in the rat insulinoma cell line, CRI-G1. J. Membarin Biol. 141, 101–112 (1994). https://doi.org/10.1007/BF00238244

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  • DOI: https://doi.org/10.1007/BF00238244

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