Increased Calcium Currents in Rat Hippocampal Neurons During Aging

  • P. W. Landfield
Part of the Bayer AG Centenary Symposium book series (BAYER)


This paper will review evidence from our laboratory which indicates that calcium currents in rat hippocampal neurons are increased with aging and that these alterations may playa key role in functional and morphological brain changes during aging. In addition, evidence will be reviewed to show that a form of calcium-dependent inactivation of calcium currents, which had been seen previously only in invertebrate neurons, is also present in mammalian hippocampal neurons. It is not clear whether changes in this inactivation mechanism are responsible for age-related changes in hippocampal calcium current (ICa), but this possibility is presently under active investigation.


Hippocampal Neuron Hippocampal Slice Calcium Current Synaptic Depression High Magnesium 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adams PR, Constanti A, Brown DA, Clark RB (1982) Intracellular Ca2+ activates a fast voltagesensitive K+ current in vertebrate sympathetic neurons. Nature (London), 296:746–749CrossRefGoogle Scholar
  2. Alger BE, Nicol RA (1980) Epileptiform burst afterhyperpolarization: clacium-dependent potassium potential in hippocampal CAl pyramidal cells. Science 210:1122–1144PubMedCrossRefGoogle Scholar
  3. Applegate MD, Landfield PW (1988) Synaptic vesicle redistribution during hippocampal frequency potentiation and depression in young and aged rats. J Neurosci 8:1096–1111PubMedGoogle Scholar
  4. Augustine GJ, Eckert R (1984) Calcium-dependent inactivation of presynaptic calcium channels. Soc Neurosci Abstr 10:194Google Scholar
  5. Ball MJ (1977) Neuronal loss, neurofibrillary tangles and granulovacuolar degeneration in the hippocampus with aging and dementia: A quantitative study. Acta Neuropatholog 37:11–118Google Scholar
  6. Bley KR, Madison D V, Tsien RW (1987) Multiple types of calcium channels in hippocampal neurons: Characterization and localization. Soc Neurosci Abstr 13:1010Google Scholar
  7. Brown DA, Griffith WH (1983) Persistent slow inward calcium current in voltage-clamped hippocampal neurones of the guinea pig. J Physiol (London) 337:303–320Google Scholar
  8. Brown TH, Johnston D (1983) Voltage-clamp analysis of mossy fiber synaptic input to hippocampal neurons. J Neurophysiol 50:487–507PubMedGoogle Scholar
  9. Buck DR, Mahoney A W, Hendricks DF (1979) Effects of cerebral intraventricular magnesium injections and a low magnesium diet on nonspecific excitability level, audiogenic seizure susceptibility and serotonin. Pharmacol Biochem Behav 10:487–491PubMedCrossRefGoogle Scholar
  10. Campbell L W, Hao SY, Landfield PW (1988) Calcium-dependent inactivation of calcium currents in hippocampal neurons: Effects of tetraethylammonium and nimodipine. Soc Neurosci Abstr 14:in pressGoogle Scholar
  11. Craik FIM (1984) Age differences in remembering. In: Squire LR, Butters N (eds) Neuropsychology of memory. Guilford Press. New York, pp 3–12Google Scholar
  12. Delgado-Escueta AV, Ward AA, Woodbury DM, Porter RJ (eds) (1986) Basic mechanisms of the epilepsies: Molecular and cellular approaches. Raven, New YorkGoogle Scholar
  13. Eckert R, Ewald D (1983) Inactivation of calcium conductance characterized by tail current measurements in neurones of Aplysia californica. J Physiol (London) 345:549–565Google Scholar
  14. Gibson GE, Peterson C (1987) Calcium and the aging nervous system. Neurobiol Aging 8:329–344PubMedCrossRefGoogle Scholar
  15. Gray R, Johnston D (1986) Multiple types of calcium channels in acutely-exposed neurons from adult hippocampus. Biophy J 49:432aGoogle Scholar
  16. Gray R, Johnston D (1987) Noradrenaline and β-adrenoceptor agonists increase activity of voltagedependent calcium channels in hippocampal neurons. Nature 327:620–622PubMedCrossRefGoogle Scholar
  17. Halliwell JW (1983) Caesium loading reveals two distinct Ca-currents in voltage-clamped guinea-pig hippocampal neurones in vitro. J Physiol (London) 341:10–11Google Scholar
  18. Johnston D, Hablitz JJ, Wilson W A (1980) Voltage clamp discloses slow inward current in hippocampal burst firing neurones. Nature 286:391–393PubMedCrossRefGoogle Scholar
  19. Katzman R (1975) Cerebrospinal fluid physiology: role of secretory and mediated transport systems. In: Tower DB (ed) The nervous system, Vol 1: The basic neurosciences. Raven Press, New York, pp 291–297Google Scholar
  20. Khachaturian ZS (1984) Towards theories of brain aging. In: Kay D, Burrows GD (eds) Handbook of studies on psychiatry and old age. Elsevier, AmsterdamGoogle Scholar
  21. Lancaster B, Adams PR (1986) Calcium-dependent current generating the afterhyperpolarization of hippocampal neurons. J Neurophysiol 55:1268–1282PubMedGoogle Scholar
  22. Landfield PW (1987) “Increased calcium current” hypothesis of brain aging. Neurobiol Aging 8:346–347PubMedCrossRefGoogle Scholar
  23. Landfield PW, Lynch G (1977) Impaired monosynaptic potentiation in in vitro hippocampal slices from aged, memory-deficient rats. J Gerontol 32:523–533PubMedGoogle Scholar
  24. Landfield PW, McGaugh JL, Lynch G (1978) Impaired synaptic potentiation processes in the hippocampus of aged, memory-deficient rats. Brain Res 150:85–101PubMedCrossRefGoogle Scholar
  25. Landfield PW, Morgan G (1984) Chronically elevating plasma Mg2+ improves hippocampal frequency potentiation and reversal learning in aged and young rats. Brain Res 322: 167–171PubMedCrossRefGoogle Scholar
  26. Landfield PW, Pitler T A (1984) Prolonged Ca2+ -dependent afterhyperpolarizations in hippocampal neurons of aged rats. Science 226: 1089–1092PubMedCrossRefGoogle Scholar
  27. Landfield PW, Pitler TA (1987) Calcium spike duration: prolongation in hippocampal neurons of aged rats. Soc Neurosci Abstr 13:718Google Scholar
  28. Landfield PW, Pitler TA, Applegate MD (1986b) The effects of high Mg2+ -to Ca2+ ratios on frequency potentiation in hippocampal slices of young and aged rats. J Neurophysiol 56:797–811PubMedGoogle Scholar
  29. Llinas R, Hess R (1976) Tetrodotoxin resistant dendritic spikes in avian Purkinje cells. Proc Natl Acad Sci USA 73:2520–2523PubMedCrossRefGoogle Scholar
  30. Martin AR (1977) Presynaptic mechanisms. In: Brookhart JM, Mountcastle VB (eds) Handbook of Physiology I: The nervous system. American Physiological Society, Bethesda, pp 329–355Google Scholar
  31. Miller RJ (1987) Calcium channels in neurones. In: Venter JC, Triggle D (eds) Structure and physiology of the slow inward calcium channel. Alan R Liss, New York, p 161Google Scholar
  32. Nayler WG, Poole-Wilson PA, Williams A (1979) Hypoxia and calcium. J Molec Cell Cardiol 11:683–706CrossRefGoogle Scholar
  33. Nowycky MC, Fox AP, Tsien RW (1985) Three types of neuronal calcium channel with different agonist sensitivity. Nature 316:440–443PubMedCrossRefGoogle Scholar
  34. Olton DS (1983) Memory functions and the hippocampus. In: Seifert W (ed) Neurobiology of the hippocampus, Academic Press, New York, pp 335–373Google Scholar
  35. Pitler TA, Landfield PW (1987 a) Probable Ca2+ -mediated inactivation of Ca2+ currents in mammalian brain neurons. Brain Res 410:147–153PubMedCrossRefGoogle Scholar
  36. Schlaepfer WW, Hasler MB (1979) Characterization of the calcium-induced disruption of neurofilaments in rat peripheral nerve. Brain Res 168:299–309PubMedCrossRefGoogle Scholar
  37. Schwartzkroin DA, Slawsky MA (1977) Probable calcium spikes in hippocampal neurones. Brain Res 135:157–161PubMedCrossRefGoogle Scholar
  38. Scriabine A (1987) Ca2+ channel ligands: Comparative pharmacology. In: Venter JC, Triggle D (eds) Structure and physiology of the slow inward calcium channel. Alan R. Liss, New York, p 51Google Scholar
  39. Smith DO (1980) Mechanisms of action potential failure at sites of axon branching in the crayfish. J Physiol (Lond) 301:243–259Google Scholar
  40. Squire LR (1986) Mechanisms of memory. Science 232:1612–1619PubMedCrossRefGoogle Scholar
  41. Storm J (1987) Action potential repolarization and a fast afterhyperpolarization in rat hippocampal pyramidal cells. J Physioi (Lond) 385:733–759Google Scholar
  42. Tomlinson BE, Henderson G (1976) Some quantitative cerebral findings in normal and demented old people. In: Terry RD, Gershon S (eds) Neurobiology of aging. Raven Press, New York, pp 183–204Google Scholar
  43. Wisniewski HM, Terry RD (1973) Morphology of the aging brain, human and animal. Prog Brain Res 40:167–186PubMedCrossRefGoogle Scholar
  44. Wong RKS, Prince DA (1981) After potential generation in hippocampal pyramidal cells. J Neurophysiol 45:87–97Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • P. W. Landfield
    • 1
  1. 1.Department of Physiology and PharmacologyBowman Gray School of Medicine, of Wake Forest UniversityWinston-SalemUSA

Personalised recommendations