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. 1984 Sep;354:139–162. doi: 10.1113/jphysiol.1984.sp015368

A novel membrane sodium current induced by injection of cyclic nucleotides into gastropod neurones.

J A Connor, P Hockberger
PMCID: PMC1193404  PMID: 6207290

Abstract

Injection of cyclic AMP (cAMP) or cyclic GMP into identifiable neurones from several different gastropod species immediately depolarized the cell membranes in a dose-dependent manner. Doses were monitored photometrically and evidence is presented for depolarizing effects following nucleotide injections of as little as 30-35 mumol. The depolarizing effect was reversible and was demonstrated under voltage clamp to be primarily the result of a nucleotide-induced, transient increase in a membrane Na current, INa (cAMP). The charge-carrying species was identified by using ion-substituted salines, reversal potential in low-Na saline, and intracellular ion-sensitive electrode measurements. The current was resistant to tetrodotoxin, ouabain and amiloride. Substituting Trisma, tetramethylammonium or bis-tris propane for Na prevented the induced current, whereas Li substitution did not. Duration of the induced current was greatly prolonged in neurones bathed in the phosphodiesterase inhibitor isobutylmethylxanthine, or following injection of any of several cAMP analogues, indicating that the reversible nature of the current stems primarily from in situ hydrolysis of the injected dose and not current inactivation. Amplitude of the induced current either remained constant or decreased over the voltage range where it could be easily measured, i.e. -30 greater than Vm greater than -100 mV, reflecting a voltage as well as a chemical sensitivity of INa (cAMP).

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Selected References

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

  1. Adams P. R., Brown D. A., Constanti A. M-currents and other potassium currents in bullfrog sympathetic neurones. J Physiol. 1982 Sep;330:537–572. doi: 10.1113/jphysiol.1982.sp014357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aldenhoff J. B., Hofmeier G., Lux H. D., Swandulla D. Stimulation of a sodium influx by cAMP in Helix neurons. Brain Res. 1983 Oct 16;276(2):289–296. doi: 10.1016/0006-8993(83)90736-9. [DOI] [PubMed] [Google Scholar]
  3. Aldrich R. W., Jr, Getting P. A., Thompson S. H. Mechanism of frequency-dependent broadening of molluscan neurone soma spikes. J Physiol. 1979 Jun;291:531–544. doi: 10.1113/jphysiol.1979.sp012829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bernier L., Castellucci V. F., Kandel E. R., Schwartz J. H. Facilitatory transmitter causes a selective and prolonged increase in adenosine 3':5'-monophosphate in sensory neurons mediating the gill and siphon withdrawal reflex in Aplysia. J Neurosci. 1982 Dec;2(12):1682–1691. doi: 10.1523/JNEUROSCI.02-12-01682.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blackshaw S. E. Dye injection and electrophysiological mapping of giant neurons in the brain of Archidoris. Proc R Soc Lond B Biol Sci. 1976 Mar 16;192(1109):393–419. doi: 10.1098/rspb.1976.0020. [DOI] [PubMed] [Google Scholar]
  6. Blaustein M. P., Russell J. M. Sodium-calcium exchange and calcium-calcium exchange in internally dialyzed squid giant axons. J Membr Biol. 1975 Jul 24;22(3-4):285–312. doi: 10.1007/BF01868176. [DOI] [PubMed] [Google Scholar]
  7. Brinley F. J., Jr, Scarpa A. Ionized magnesium concentration in axoplasm of dialyzed squid axons. FEBS Lett. 1975 Jan 15;50(1):82–85. doi: 10.1016/0014-5793(75)81046-5. [DOI] [PubMed] [Google Scholar]
  8. Brown D. A., Adams P. R. Muscarinic suppression of a novel voltage-sensitive K+ current in a vertebrate neurone. Nature. 1980 Feb 14;283(5748):673–676. doi: 10.1038/283673a0. [DOI] [PubMed] [Google Scholar]
  9. Brunelli M., Castellucci V., Kandel E. R. Synaptic facilitation and behavioral sensitization in Aplysia: possible role of serotonin and cyclic AMP. Science. 1976 Dec 10;194(4270):1178–1181. doi: 10.1126/science.186870. [DOI] [PubMed] [Google Scholar]
  10. Carpenter D. O., Alving B. O. A contribution of an electrogenic Na+ pump to membrane potential in Aplysia neurons. J Gen Physiol. 1968 Jul;52(1):1–21. doi: 10.1085/jgp.52.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cedar H., Schwartz J. H. Cyclic adenosine monophosphate in the nervous system of Aplysia californica. II. Effect of serotonin and dopamine. J Gen Physiol. 1972 Nov;60(5):570–587. doi: 10.1085/jgp.60.5.570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Connor J. A. Calcium current in molluscan neurones: measurement under conditions which maximize its visibility. J Physiol. 1979 Jan;286:41–60. doi: 10.1113/jphysiol.1979.sp012606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Connor J. A., Hockberger P. Intracellular pH changes induced by injection of cyclic nucleotides into gastropod neurones. J Physiol. 1984 Sep;354:163–172. doi: 10.1113/jphysiol.1984.sp015369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Connor J. A., Stevens C. F. Inward and delayed outward membrane currents in isolated neural somata under voltage clamp. J Physiol. 1971 Feb;213(1):1–19. doi: 10.1113/jphysiol.1971.sp009364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Deterre P., Paupardin-Tritsch D., Bockaert J., Gerschenfeld H. M. Role of cyclic AMP in a serotonin-evoked slow inward current in snail neurones. Nature. 1981 Apr 30;290(5809):783–785. doi: 10.1038/290783a0. [DOI] [PubMed] [Google Scholar]
  16. Deterre P., Paupardin-Tritsch D., Bockaert J., Gerschenfeld H. M. cAMP-mediated decrease in K+ conductance evoked by serotonin and dopamine in the same neuron: a biochemical and physiological single-cell study. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7934–7938. doi: 10.1073/pnas.79.24.7934. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Dworkin M., Keller K. H. Solubility and diffusion coefficient of adenosine 3':5'-monophosphate. J Biol Chem. 1977 Feb 10;252(3):864–865. [PubMed] [Google Scholar]
  18. Eaton D. C., Russell J. M., Brown A. M. Ionic permeabilities of an Aplysia giant neuron. J Membr Biol. 1975;21(3-4):353–374. doi: 10.1007/BF01941076. [DOI] [PubMed] [Google Scholar]
  19. Gallagher J. P., Shinnick-Gallagher P. Cyclic nucleotides injected intracellularly into rat superior cervical ganglion cells. Science. 1977 Nov 25;198(4319):851–852. doi: 10.1126/science.199943. [DOI] [PubMed] [Google Scholar]
  20. Geduldig D., Junge D. Sodium and calcium components of action potentials in the Aplysia giant neurone. J Physiol. 1968 Dec;199(2):347–365. doi: 10.1113/jphysiol.1968.sp008657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Green D. J., Gillette R. Patch- and voltage-clamp analysis of cyclic AMP-stimulated inward current underlying neurone bursting. Nature. 1983 Dec 22;306(5945):784–785. doi: 10.1038/306784a0. [DOI] [PubMed] [Google Scholar]
  22. Hartzell H. C. Mechanisms of slow postsynaptic potentials. Nature. 1981 Jun 18;291(5816):539–544. doi: 10.1038/291539a0. [DOI] [PubMed] [Google Scholar]
  23. Hashiguchi T., Kobayashi H., Tosaka T., Libet B. Two muscarinic depolarizing mechanisms in mammalian sympathetic neurons. Brain Res. 1982 Jun 24;242(2):378–382. doi: 10.1016/0006-8993(82)90329-8. [DOI] [PubMed] [Google Scholar]
  24. Hockberger P., Connor J. A. Intracellular calcium measurements with arsenazo III during cyclic AMP injections into molluscan neurons. Science. 1983 Feb 18;219(4586):869–871. doi: 10.1126/science.6297009. [DOI] [PubMed] [Google Scholar]
  25. Kaczmarek L. K., Strumwasser F. The expression of long lasting afterdischarge by isolated Aplysia bag cell neurons. J Neurosci. 1981 Jun;1(6):626–634. doi: 10.1523/JNEUROSCI.01-06-00626.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kehoe J. S., Marty A. Certain slow synaptic responses: their properties and possible underlying mechanisms. Annu Rev Biophys Bioeng. 1980;9:437–465. doi: 10.1146/annurev.bb.09.060180.002253. [DOI] [PubMed] [Google Scholar]
  27. Klein M., Kandel E. R. Mechanism of calcium current modulation underlying presynaptic facilitation and behavioral sensitization in Aplysia. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6912–6916. doi: 10.1073/pnas.77.11.6912. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Klein M., Kandel E. R. Presynaptic modulation of voltage-dependent Ca2+ current: mechanism for behavioral sensitization in Aplysia californica. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3512–3516. doi: 10.1073/pnas.75.7.3512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kobayashi H., Libet B. Generation of slow postsynaptic potentials without increases in ionic conductance. Proc Natl Acad Sci U S A. 1968 Aug;60(4):1304–1311. doi: 10.1073/pnas.60.4.1304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Krnjevic K., Van Meter W. G. Cyclic nucleotides in spinal cells. Can J Physiol Pharmacol. 1976 Jun;54(3):416–421. doi: 10.1139/y76-059. [DOI] [PubMed] [Google Scholar]
  31. Liberman E. A., Minina S. V., Shklovskii-Kordi N. E. Gipoteze o roli sluchainykh sviazei mezhdu nervnymi kletkami mozga. Biofizika. 1981 Jan-Feb;26(1):153–157. [PubMed] [Google Scholar]
  32. Madison D. V., Nicoll R. A. Noradrenaline blocks accommodation of pyramidal cell discharge in the hippocampus. Nature. 1982 Oct 14;299(5884):636–638. doi: 10.1038/299636a0. [DOI] [PubMed] [Google Scholar]
  33. Magleby K. L., Stevens C. F. A quantitative description of end-plate currents. J Physiol. 1972 May;223(1):173–197. doi: 10.1113/jphysiol.1972.sp009840. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Nathanson J. A. Cyclic nucleotides and nervous system function. Physiol Rev. 1977 Apr;57(2):157–256. doi: 10.1152/physrev.1977.57.2.157. [DOI] [PubMed] [Google Scholar]
  35. Partridge L. D., Stevens C. F. A mechanism for spike frequency adaptation. J Physiol. 1976 Apr;256(2):315–332. doi: 10.1113/jphysiol.1976.sp011327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Partridge L. D., Thompson S. H., Smith S. J., Connor J. A. Current-voltage relationships of repetitively firing neurons. Brain Res. 1979 Mar 23;164:69–79. doi: 10.1016/0006-8993(79)90007-6. [DOI] [PubMed] [Google Scholar]
  37. Pellmar T. C. Ionic mechanism of a voltage-dependent current elicited by cyclic AMP. Cell Mol Neurobiol. 1981 Mar;1(1):87–97. doi: 10.1007/BF00736041. [DOI] [PubMed] [Google Scholar]
  38. Rodbell M. The role of hormone receptors and GTP-regulatory proteins in membrane transduction. Nature. 1980 Mar 6;284(5751):17–22. doi: 10.1038/284017a0. [DOI] [PubMed] [Google Scholar]
  39. Seamon K. B., Padgett W., Daly J. W. Forskolin: unique diterpene activator of adenylate cyclase in membranes and in intact cells. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3363–3367. doi: 10.1073/pnas.78.6.3363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Shimahara T., Tauc L. Cyclic AMP induced by serotonin modulates the activity of an identified synapse in Aplysia by facilitating the active permeability to calcium. Brain Res. 1977 May 20;127(1):168–172. doi: 10.1016/0006-8993(77)90389-4. [DOI] [PubMed] [Google Scholar]
  41. Shoemaker W. J., Balentine L. T., Siggins G. R., Hoffer B. J., Henriksen S. J., Bloom F. E. Characteristics of the release of adenosine 3':5'-monophosphate from micropipets by microiontophoresis. J Cyclic Nucleotide Res. 1975;1(2):97–106. [PubMed] [Google Scholar]
  42. Siegelbaum S. A., Camardo J. S., Kandel E. R. Serotonin and cyclic AMP close single K+ channels in Aplysia sensory neurones. Nature. 1982 Sep 30;299(5882):413–417. doi: 10.1038/299413a0. [DOI] [PubMed] [Google Scholar]
  43. Smith T. G., Jr, Barker J. L., Gainer H. Requirements for bursting pacemaker potential activity in molluscan neurones. Nature. 1975 Feb 6;253(5491):450–452. doi: 10.1038/253450a0. [DOI] [PubMed] [Google Scholar]
  44. Thomas R. C. Membrane current and intracellular sodium changes in a snail neurone during extrusion of injected sodium. J Physiol. 1969 Apr;201(2):495–514. doi: 10.1113/jphysiol.1969.sp008769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Treistman S. N., Levitan I. B. Alteration of electrical activity in molluscan neurones by cyclic nucleotides and peptide factors. Nature. 1976 May 6;261(5555):62–64. doi: 10.1038/261062a0. [DOI] [PubMed] [Google Scholar]
  46. Tsien R. W. Adrenaline-like effects of intracellular iontophoresis of cyclic AMP in cardiac Purkinje fibres. Nat New Biol. 1973 Sep 26;245(143):120–122. doi: 10.1038/newbio245120a0. [DOI] [PubMed] [Google Scholar]
  47. Wilson W. A., Wachtel H. Negative resistance characteristic essential for the maintenance of slow oscillations in bursting neurons. Science. 1974 Dec 6;186(4167):932–934. doi: 10.1126/science.186.4167.932. [DOI] [PubMed] [Google Scholar]
  48. Yamazaki A., Bartucca F., Ting A., Bitensky M. W. Reciprocal effects of an inhibitory factor on catalytic activity and noncatalytic cGMP binding sites of rod phosphodiesterase. Proc Natl Acad Sci U S A. 1982 Jun;79(12):3702–3706. doi: 10.1073/pnas.79.12.3702. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Yau K. W., McNaughton P. A., Hodgkin A. L. Effect of ions on the light-sensitive current in retinal rods. Nature. 1981 Aug 6;292(5823):502–505. doi: 10.1038/292502a0. [DOI] [PubMed] [Google Scholar]

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