Skip to main content
PMC home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1997 Nov 15;505(Pt 1):65–76. doi: 10.1111/j.1469-7793.1997.065bc.x

Characterization of a nicotinamide-adenine dinucleotide-dependent cation channel in the CRI-G1 rat insulinoma cell line.

P S Herson 1, K A Dulock 1, M L Ashford 1
PMCID: PMC1160094  PMID: 9409472

Abstract

1. Cell-free excised membrane patches were used to examine the properties of a novel nicotinamide-adenine dinucleotide (beta-NAD+)-activated ion channel in the rat insulin-secreting cell line, CRI-G1. 2. In inside-out recordings, beta-NAD+ (0.05-1.0 mM) induced the appearance of a channel characterized by extremely slow kinetics, with mean open times in the range of seconds. The estimated EC50 for activation was 114 microM. Channel activity declined with time (run-down) following activation by beta-NAD+ in excised patches and this was not prevented by intracellular application of trypsin. 3. The single channel current-voltage relationship was linear with a conductance of 74 pS in symmetrical NaCl. The channel appears equally permeable to Na+, K+ and Cs+, exhibits an appreciable permeability to Ca2+, Mg2+ and Ba2+, but excludes anions. 4. The channel displays an unusual voltage sensitivity, with an abrupt increase in open-state probability at depolarized voltages. 5. Channel opening, in the presence of beta-NAD+, required both Ca2+ and Mg2+ to be present at the internal side of the membrane. Activation by Ca2+ required a concentration of at least 10 microM and was maximal at 0.1 mM. Ba2+ did not substitute for Ca2+ in inducing channel activity nor did it inhibit activation by Ca2+. Increasing the concentration of intracellular Mg2+ stabilized the open state of NAD(+)-activated channels. 6. The non-selective cation channel reported here differs in its gating and modulatory characteristics from non-selective cation channels described in other tissues. This channel may play a role in the pathophysiological responses of beta-cells to oxidative stress.

Full text

PDF
65

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bevan S., Gray P. T., Ritchie J. M. A calcium-activated cation-selective channel in rat cultured Schwann cells. Proc R Soc Lond B Biol Sci. 1984 Sep 22;222(1228):349–355. doi: 10.1098/rspb.1984.0068. [DOI] [PubMed] [Google Scholar]
  2. Carrington C. A., Rubery E. D., Pearson E. C., Hales C. N. Five new insulin-producing cell lines with differing secretory properties. J Endocrinol. 1986 May;109(2):193–200. doi: 10.1677/joe.0.1090193. [DOI] [PubMed] [Google Scholar]
  3. Chernaya G., Vázquez M., Reeves J. P. Sodium-calcium exchange and store-dependent calcium influx in transfected chinese hamster ovary cells expressing the bovine cardiac sodium-calcium exchanger. Acceleration of exchange activity in thapsigargin-treated cells. J Biol Chem. 1996 Mar 8;271(10):5378–5385. doi: 10.1074/jbc.271.10.5378. [DOI] [PubMed] [Google Scholar]
  4. Dunne M. J., Findlay I., Petersen O. H. Effects of pyridine nucleotides on the gating of ATP-sensitive potassium channels in insulin-secreting cells. J Membr Biol. 1988 Jun;102(3):205–216. doi: 10.1007/BF01925714. [DOI] [PubMed] [Google Scholar]
  5. Gutteridge J. M. Free radicals in disease processes: a compilation of cause and consequence. Free Radic Res Commun. 1993;19(3):141–158. doi: 10.3109/10715769309111598. [DOI] [PubMed] [Google Scholar]
  6. Guérineau N. C., Bossu J. L., Gähwiler B. H., Gerber U. Activation of a nonselective cationic conductance by metabotropic glutamatergic and muscarinic agonists in CA3 pyramidal neurons of the rat hippocampus. J Neurosci. 1995 Jun;15(6):4395–4407. doi: 10.1523/JNEUROSCI.15-06-04395.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hedeskov C. J., Capito K., Thams P. Cytosolic ratios of free [NADPH]/[NADP+] and [NADH]/[NAD+] in mouse pancreatic islets, and nutrient-induced insulin secretion. Biochem J. 1987 Jan 1;241(1):161–167. doi: 10.1042/bj2410161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Herson P. S., Ashford M. L. Activation of a novel non-selective cation channel by alloxan and H2O2 in the rat insulin-secreting cell line CRI-G1. J Physiol. 1997 May 15;501(Pt 1):59–66. doi: 10.1111/j.1469-7793.1997.059bo.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Holz G. G., 4th, Leech C. A., Habener J. F. Activation of a cAMP-regulated Ca(2+)-signaling pathway in pancreatic beta-cells by the insulinotropic hormone glucagon-like peptide-1. J Biol Chem. 1995 Jul 28;270(30):17749–17757. [PMC free article] [PubMed] [Google Scholar]
  10. Inoue M., Imanaga I. Mechanism of activation of nonselective cation channels by putative M4 muscarinic receptor in guinea-pig chromaffin cells. Br J Pharmacol. 1995 Jan;114(2):419–427. doi: 10.1111/j.1476-5381.1995.tb13243.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kozlowski R. Z., Ashford M. L. ATP-sensitive K(+)-channel run-down is Mg2+ dependent. Proc R Soc Lond B Biol Sci. 1990 Jun 22;240(1298):397–410. doi: 10.1098/rspb.1990.0044. [DOI] [PubMed] [Google Scholar]
  12. Lee K., Ozanne S. E., Hales C. N., Ashford M. L. Mg(2+)-dependent inhibition of KATP by sulphonylureas in CRI-G1 insulin-secreting cells. Br J Pharmacol. 1994 Feb;111(2):632–640. doi: 10.1111/j.1476-5381.1994.tb14783.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lee K., Ozanne S. E., Rowe I. C., Hales C. N., Ashford M. L. The effects of trypsin on ATP-sensitive potassium channel properties and sulfonylurea receptors in the CRI-G1 insulin-secreting cell line. Mol Pharmacol. 1994 Jul;46(1):176–185. [PubMed] [Google Scholar]
  14. Lee S., Park M., So I., Earm Y. E. NADH and NAD modulates Ca(2+)-activated K+ channels in small pulmonary arterial smooth muscle cells of the rabbit. Pflugers Arch. 1994 Jun;427(3-4):378–380. doi: 10.1007/BF00374548. [DOI] [PubMed] [Google Scholar]
  15. Lewis C. A. Ion-concentration dependence of the reversal potential and the single channel conductance of ion channels at the frog neuromuscular junction. J Physiol. 1979 Jan;286:417–445. doi: 10.1113/jphysiol.1979.sp012629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Llinás R., Sugimori M., Silver R. B. Microdomains of high calcium concentration in a presynaptic terminal. Science. 1992 May 1;256(5057):677–679. doi: 10.1126/science.1350109. [DOI] [PubMed] [Google Scholar]
  17. Matschinsky F. M., Ghosh A. K., Meglasson M. D., Prentki M., June V., von Allman D. Metabolic concomitants in pure, pancreatic beta cells during glucose-stimulated insulin secretion. J Biol Chem. 1986 Oct 25;261(30):14057–14061. [PubMed] [Google Scholar]
  18. McKillen H. C., Davies N. W., Stanfield P. R., Standen N. B. The effect of intracellular anions on ATP-dependent potassium channels of rat skeletal muscle. J Physiol. 1994 Sep 15;479(Pt 3):341–351. doi: 10.1113/jphysiol.1994.sp020300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. McManus O. B. Calcium-activated potassium channels: regulation by calcium. J Bioenerg Biomembr. 1991 Aug;23(4):537–560. doi: 10.1007/BF00785810. [DOI] [PubMed] [Google Scholar]
  20. Ohno-Shosaku T., Zünkler B. J., Trube G. Dual effects of ATP on K+ currents of mouse pancreatic beta-cells. Pflugers Arch. 1987 Feb;408(2):133–138. doi: 10.1007/BF00581342. [DOI] [PubMed] [Google Scholar]
  21. Olanow C. W., Arendash G. W. Metals and free radicals in neurodegeneration. Curr Opin Neurol. 1994 Dec;7(6):548–558. doi: 10.1097/00019052-199412000-00013. [DOI] [PubMed] [Google Scholar]
  22. Proks P., Ashcroft F. M. Modification of K-ATP channels in pancreatic beta-cells by trypsin. Pflugers Arch. 1993 Jun;424(1):63–72. doi: 10.1007/BF00375103. [DOI] [PubMed] [Google Scholar]
  23. Reale V., Hales C. N., Ashford M. L. The effects of pyridine nucleotides on the activity of a calcium-activated nonselective cation channel in the rat insulinoma cell line, CRI-G1. J Membr Biol. 1994 Dec;142(3):299–307. doi: 10.1007/BF00233437. [DOI] [PubMed] [Google Scholar]
  24. Sturgess N. C., Hales C. N., Ashford M. L. Calcium and ATP regulate the activity of a non-selective cation channel in a rat insulinoma cell line. Pflugers Arch. 1987 Aug;409(6):607–615. doi: 10.1007/BF00584661. [DOI] [PubMed] [Google Scholar]
  25. Thomson A. M. Glycine is a coagonist at the NMDA receptor/channel complex. Prog Neurobiol. 1990;35(1):53–74. doi: 10.1016/0301-0082(90)90040-n. [DOI] [PubMed] [Google Scholar]
  26. Thorn P., Petersen O. H. Activation of nonselective cation channels by physiological cholecystokinin concentrations in mouse pancreatic acinar cells. J Gen Physiol. 1992 Jul;100(1):11–25. doi: 10.1085/jgp.100.1.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Van den Abbeele T., Tran Ba Huy P., Teulon J. Modulation by purines of calcium-activated non-selective cation channels in the outer hair cells of the guinea-pig cochlea. J Physiol. 1996 Jul 1;494(Pt 1):77–89. doi: 10.1113/jphysiol.1996.sp021477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Yau K. W. Cyclic nucleotide-gated channels: an expanding new family of ion channels. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3481–3483. doi: 10.1073/pnas.91.9.3481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Zilberter Y., Burnashev N., Papin A., Portnov V., Khodorov B. Gating kinetics of ATP-sensitive single potassium channels in myocardial cells depends on electromotive force. Pflugers Arch. 1988 May;411(5):584–589. doi: 10.1007/BF00582382. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES