Skip to main content
PMC home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1995 Jan 15;482(Pt 2):317–323. doi: 10.1113/jphysiol.1995.sp020520

Nicotinamide-adenine dinucleotide regulates muscarinic receptor-coupled K+ (M) channels in rodent NG108-15 cells.

H Higashida 1, J Robbins 1, A Egorova 1, M Noda 1, M Taketo 1, N Ishizaka 1, S Takasawa 1, H Okamoto 1, D A Brown 1
PMCID: PMC1157731  PMID: 7714825

Abstract

1. The possible role of nicotinamide-adenine dinucleotide (NAD+) and cyclic adenosine diphosphate ribose (cADPR) as regulators of M-type K+ currents (IK(M)) has been studied in whole-cell patch-clamped NG108-15 mouse neuroblastoma x rat glioma cells that had been transformed to express m1 muscarinic acetylcholine receptors (mAChRs). 2. Pre-incubation of NG108-15 cells for 6-8 h with streptozotocin (2-5 mM) reduced NAD+ levels by 40-50%. Nicotinamide (2-5 mM) increased NAD+ levels and prevented depletion by streptozotocin. 3. Streptozotocin pretreatment reduced the inhibition of IK(M) produced by 100 microM acetylcholine (ACh) from 51.6 +/- 7.0 to 29.1 +/- 7.5%. This was prevented by simultaneous pre-incubation with 2 mM nicotinamide or by adding 2 mM NAD+ to the pipette solution. Neither procedure significantly affected the initial amplitude of IK(M). 4. Inclusion of 2 microM cADPR in the pipette solution induced a slow loss of IK(M) with a time constant of about 20 min. 5. It is concluded that mAChR-induced inhibition of IK(M) requires intracellular NAD+. This might be needed for the formation of cADPR as a regulator or messenger for IK(M) inhibition.

Full text

PDF
317

Selected References

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

  1. Caulfield M. P., Jones S., Vallis Y., Buckley N. J., Kim G. D., Milligan G., Brown D. A. Muscarinic M-current inhibition via G alpha q/11 and alpha-adrenoceptor inhibition of Ca2+ current via G alpha o in rat sympathetic neurones. J Physiol. 1994 Jun 15;477(Pt 3):415–422. doi: 10.1113/jphysiol.1994.sp020203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Donnelly L. E., Boyd R. S., MacDermot J. Gs alpha is a substrate for mono(ADP-ribosyl)transferase of NG108-15 cells. ADP-ribosylation regulates Gs alpha activity and abundance. Biochem J. 1992 Nov 15;288(Pt 1):331–336. doi: 10.1042/bj2880331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Fukuda K., Higashida H., Kubo T., Maeda A., Akiba I., Bujo H., Mishina M., Numa S. Selective coupling with K+ currents of muscarinic acetylcholine receptor subtypes in NG108-15 cells. Nature. 1988 Sep 22;335(6188):355–358. doi: 10.1038/335355a0. [DOI] [PubMed] [Google Scholar]
  4. Galione A., Lee H. C., Busa W. B. Ca(2+)-induced Ca2+ release in sea urchin egg homogenates: modulation by cyclic ADP-ribose. Science. 1991 Sep 6;253(5024):1143–1146. doi: 10.1126/science.1909457. [DOI] [PubMed] [Google Scholar]
  5. Galione A., White A., Willmott N., Turner M., Potter B. V., Watson S. P. cGMP mobilizes intracellular Ca2+ in sea urchin eggs by stimulating cyclic ADP-ribose synthesis. Nature. 1993 Sep 30;365(6445):456–459. doi: 10.1038/365456a0. [DOI] [PubMed] [Google Scholar]
  6. Higashida H., Brown D. A. Two polyphosphatidylinositide metabolites control two K+ currents in a neuronal cell. 1986 Sep 25-Oct 1Nature. 323(6086):333–335. doi: 10.1038/323333a0. [DOI] [PubMed] [Google Scholar]
  7. Hua S. Y., Tokimasa T., Takasawa S., Furuya Y., Nohmi M., Okamoto H., Kuba K. Cyclic ADP-ribose modulates Ca2+ release channels for activation by physiological Ca2+ entry in bullfrog sympathetic neurons. Neuron. 1994 May;12(5):1073–1079. doi: 10.1016/0896-6273(94)90315-8. [DOI] [PubMed] [Google Scholar]
  8. Kim H., Jacobson E. L., Jacobson M. K. Synthesis and degradation of cyclic ADP-ribose by NAD glycohydrolases. Science. 1993 Sep 3;261(5126):1330–1333. doi: 10.1126/science.8395705. [DOI] [PubMed] [Google Scholar]
  9. Kimura Y., Higashida H. Dissection of bradykinin-evoked responses by buffering intracellular Ca2+ in neuroblastoma x glioma hybrid NG108-15 cells. Neurosci Res. 1992 Nov;15(3):213–220. doi: 10.1016/0168-0102(92)90007-y. [DOI] [PubMed] [Google Scholar]
  10. Neher E., Marty A., Fukuda K., Kubo T., Numa S. Intracellular calcium release mediated by two muscarinic receptor subtypes. FEBS Lett. 1988 Nov 21;240(1-2):88–94. doi: 10.1016/0014-5793(88)80345-4. [DOI] [PubMed] [Google Scholar]
  11. Nisselbaum J. S., Green S. A simple ultramicro method for determination of pyridine nucleotides in tissues. Anal Biochem. 1969 Feb;27(2):212–217. doi: 10.1016/0003-2697(69)90025-6. [DOI] [PubMed] [Google Scholar]
  12. Robbins J., Marsh S. J., Brown D. A. On the mechanism of M-current inhibition by muscarinic m1 receptors in DNA-transfected rodent neuroblastoma x glioma cells. J Physiol. 1993 Sep;469:153–178. doi: 10.1113/jphysiol.1993.sp019809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Schein P. S., Loftus S. Streptozotocin: depression of mouse liver pyridine nucleotides. Cancer Res. 1968 Aug;28(8):1501–1506. [PubMed] [Google Scholar]
  14. Selyanko A. A., Stansfeld C. E., Brown D. A. Closure of potassium M-channels by muscarinic acetylcholine-receptor stimulants requires a diffusible messenger. Proc Biol Sci. 1992 Nov 23;250(1328):119–125. doi: 10.1098/rspb.1992.0139. [DOI] [PubMed] [Google Scholar]
  15. Stansfeld C. E., Marsh S. J., Gibb A. J., Brown D. A. Identification of M-channels in outside-out patches excised from sympathetic ganglion cells. Neuron. 1993 Apr;10(4):639–654. doi: 10.1016/0896-6273(93)90166-o. [DOI] [PubMed] [Google Scholar]
  16. Takasawa S., Nata K., Yonekura H., Okamoto H. Cyclic ADP-ribose in insulin secretion from pancreatic beta cells. Science. 1993 Jan 15;259(5093):370–373. doi: 10.1126/science.8420005. [DOI] [PubMed] [Google Scholar]
  17. White A. M., Watson S. P., Galione A. Cyclic ADP-ribose-induced Ca2+ release from rat brain microsomes. FEBS Lett. 1993 Mar 8;318(3):259–263. doi: 10.1016/0014-5793(93)80524-x. [DOI] [PubMed] [Google Scholar]
  18. Wilk-Blaszczak M. A., Gutowski S., Sternweis P. C., Belardetti F. Bradykinin modulates potassium and calcium currents in neuroblastoma hybrid cells via different pertussis toxin-insensitive pathways. Neuron. 1994 Jan;12(1):109–116. doi: 10.1016/0896-6273(94)90156-2. [DOI] [PubMed] [Google Scholar]
  19. Yamamoto H., Uchigata Y., Okamoto H. Streptozotocin and alloxan induce DNA strand breaks and poly(ADP-ribose) synthetase in pancreatic islets. Nature. 1981 Nov 19;294(5838):284–286. doi: 10.1038/294284a0. [DOI] [PubMed] [Google Scholar]

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

RESOURCES