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PMID: 8815908 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Aging changes in voltage-gated calcium currents in hippocampal CA1 neurons.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 16 ·No. 19 ·1996-10-01 ·Pages 6286-95

Campbell LW, Hao SY, Thibault O, Blalock EM, Landfield PW

Abstract

Previous current-clamp studies in rat hippocampal slice CA1 neurons have found aging-related increases in long-lasting calcium (Ca)-dependent and Ca-mediated potentials. These changes could reflect an increase in Ca influx through voltage-gated Ca channels but also could reflect a change in potassium currents. Moreover, if altered Ca influx is involved, it is nuclear whether it arises from generally increased Ca channel activity, lower threshold, or reduced inactivation. To analyze the basis for altered Ca potentials, whole-cell voltage-clamp studies of CA1 hippocampal neurons were performed in nondissociated hippocampal slices of adult (3- to 5-month-old) and aged (25- to 26-month-old) rats. An aging-related increase was found in high-threshold Ca and barium (Ba) currents, particularly in the less variable, slowly inactivating (late) current at the end of a depolarization step. Input resistance of neurons did not differ between age groups. In steady-state inactivation and repetitive-pulse protocols, inactivation of Ca and Ba currents was not reduced and, in some cases, was slightly greater in aged neurons, apparently because of larger inward current. The current blocked by nimodipine was greater in aged neurons, indicating that some of the aging increase was in L-type currents. These results indicate that whole-cell Ca currents are increased with aging in CA1 neurons, apparently attributable to greater channel activity rather than to reduced inactivation. The elevated Ca influx seems likely to play a role in impaired function and enhanced susceptibility to neurotoxic influences.

MeSH Terms
Action Potentials Aging/physiology Animals Calcium/physiology Calcium Channels/physiology Electric Conductivity Electrophysiology Hippocampus/cytology,physiology Homeostasis Ion Channel Gating Male Neurons/physiology Rats Rats, Inbred F344
Chemicals
Calcium Channels Calcium
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Campbell L W
Department of Pharmacology, College of Medicine, University of Kentucky, Lexington 40536, USA.
Hao S Y
Thibault O
Blalock E M
Landfield P W
References (83)
83 references, click to expand
  1. Neuron numbers and dendritic extent in normal aging and Alzheimer's disease.
    Neurobiol Aging. 1987 Nov-Dec;8(6):521-45 PMID: 3323927
  2. Gating of L-type Ca2+ channels in embryonic chick ventricle cells: dependence on voltage, current and channel density.
    J Physiol. 1991 Nov;443:307-34 PMID: 1668339
  3. Regulation of calcium levels in brain tissue from adult and aged rats.
    Mech Ageing Dev. 1992 Mar 1;62(3):291-306 PMID: 1583914
  4. Hippocampal neurobiological mechanisms of age-related memory dysfunction.
    Neurobiol Aging. 1988 Sep-Dec;9(5-6):571-9 PMID: 3062468
  5. Calcium imaging in hippocampal neurons using confocal microscopy.
    Ann N Y Acad Sci. 1994 Dec 15;747:313-24 PMID: 7847680
  6. Ion transport systems and Ca2+ regulation in aging neurons.
    Ann N Y Acad Sci. 1994 Dec 15;747:407-18 PMID: 7847687
  7. Effects of dihydropyridines on calcium currents in CA3 pyramidal cells in slice cultures of rat hippocampus.
    Neuroscience. 1987 Mar;20(3):731-8 PMID: 2439942
  8. Multiple types of high-threshold calcium channels in rabbit sensory neurons: high-affinity block of neuronal L-type by nimodipine.
    J Neurosci. 1992 Jun;12(6):2225-34 PMID: 1318957
  9. Classes of calcium channels in vertebrate cells.
    Annu Rev Physiol. 1989;51:367-84 PMID: 2540697
  10. Physiological compensation for loss of afferent synapses in rat hippocampal granule cells during senescence.
    J Physiol. 1980 Dec;309:473-85 PMID: 7252877
  11. Multiple components of calcium current in acutely dissociated dentate gyrus granule neurons.
    J Neurophysiol. 1994 Aug;72(2):762-77 PMID: 7983534
  12. Age-dependent alterations in synaptic membrane systems for Ca2+ regulation.
    Mech Ageing Dev. 1984 Apr-May;25(1-2):215-25 PMID: 6144821
  13. Molecular diversity of voltage-dependent Ca2+ channels.
    Trends Pharmacol Sci. 1991 Sep;12(9):349-54 PMID: 1659003
  14. Multiple types of neuronal calcium channels and their selective modulation.
    Trends Neurosci. 1988 Oct;11(10):431-8 PMID: 2469160
  15. Photolytic manipulation of Ca2+ and the time course of slow, Ca(2+)-activated K+ current in rat hippocampal neurones.
    J Physiol. 1994 Mar 1;475(2):229-39 PMID: 8021830
  16. Interpretation of voltage-clamp measurements in hippocampal neurons.
    J Neurophysiol. 1983 Aug;50(2):464-86 PMID: 6310063
  17. Increased hippocampal Ca2+ channel activity in brain aging and dementia. Hormonal and pharmacologic modulation.
    Ann N Y Acad Sci. 1994 Dec 15;747:351-64 PMID: 7847683
  18. Prolonged Ca2+-dependent afterhyperpolarizations in hippocampal neurons of aged rats.
    Science. 1984 Nov 30;226(4678):1089-92 PMID: 6494926
  19. Synaptic activation of voltage-gated channels in the dendrites of hippocampal pyramidal neurons.
    Science. 1995 Apr 14;268(5208):301-4 PMID: 7716525
  20. AHP reductions in rabbit hippocampal neurons during conditioning correlate with acquisition of the learned response.
    Brain Res. 1988 Oct 11;462(1):118-25 PMID: 3179727
  21. Enhanced acquisition of reversal training in a spatial learning task in rats treated with chronic nimodipine.
    Pharmacol Biochem Behav. 1993 Apr;44(4):827-35 PMID: 8469695
  22. Age-related alterations in monoamine release from rat striatum: an in vivo electrochemical study.
    Neurobiol Aging. 1986 Mar-Apr;7(2):77-82 PMID: 3960266
  23. Potassium currents in hippocampal pyramidal cells.
    Prog Brain Res. 1990;83:161-87 PMID: 2203097
  24. Inhibition of calcium channels in rat CA3 pyramidal neurons by a metabotropic glutamate receptor.
    J Neurosci. 1992 Nov;12(11):4358-71 PMID: 1359036
  25. Pharmacological dissection of multiple types of Ca2+ channel currents in rat cerebellar granule neurons.
    J Neurosci. 1995 Apr;15(4):2995-3012 PMID: 7722641
  26. Ca2+ channels in rat central and peripheral neurons: high-threshold current resistant to dihydropyridine blockers and omega-conotoxin.
    Neuron. 1991 Feb;6(2):269-80 PMID: 1847065
  27. The effects of high Mg2+-to-Ca2+ ratios on frequency potentiation in hippocampal slices of young and aged rats.
    J Neurophysiol. 1986 Sep;56(3):797-811 PMID: 3783221
  28. Elementary properties and pharmacological sensitivities of calcium channels in mammalian peripheral neurons.
    Neuron. 1989 May;2(5):1453-63 PMID: 2560643
  29. Synaptosomal calcium metabolism during hypoxia and 3,4-diaminopyridine treatment.
    J Neurochem. 1984 Jan;42(1):248-53 PMID: 6689690
  30. Permeation and block of N-methyl-D-aspartic acid receptor channels by divalent cations in mouse cultured central neurones.
    J Physiol. 1987 Dec;394:501-27 PMID: 2451020
  31. Nimodipine increases excitability of rabbit CA1 pyramidal neurons in an age- and concentration-dependent manner.
    J Neurophysiol. 1992 Dec;68(6):2100-9 PMID: 1491260
  32. Increase in single L-type calcium channels in hippocampal neurons during aging.
    Science. 1996 May 17;272(5264):1017-20 PMID: 8638124
  33. Age-related reduction in responses of rat hippocampal neurons to locally applied monoamines.
    Neurobiol Aging. 1988 Mar-Apr;9(2):173-9 PMID: 3374734
  34. Voltage-sensitive Ca2+ channels.
    J Biol Chem. 1992 Jan 25;267(3):1403-6 PMID: 1309781
  35. Blocking and isolation of a calcium channel from neurons in mammals and cephalopods utilizing a toxin fraction (FTX) from funnel-web spider poison.
    Proc Natl Acad Sci U S A. 1989 Mar;86(5):1689-93 PMID: 2537980
  36. Kinetic and pharmacological properties distinguishing three types of calcium currents in chick sensory neurones.
    J Physiol. 1987 Dec;394:149-72 PMID: 2451016
  37. Corticosteroid modulation of hippocampal potentials: increased effect with aging.
    Science. 1989 Sep 29;245(4925):1505-9 PMID: 2781293
  38. Inactivation of a slow Ca2+ current in CA1 neurones of the adult rat hippocampal slice.
    Neurosci Lett. 1990 Mar 26;111(1-2):102-8 PMID: 2110633
  39. 'Increased calcium-current' hypothesis of brain aging.
    Neurobiol Aging. 1987 Jul-Aug;8(4):346-7 PMID: 3627350
  40. Synaptically activated increases in Ca2+ concentration in hippocampal CA1 pyramidal cells are primarily due to voltage-gated Ca2+ channels.
    Neuron. 1992 Dec;9(6):1163-73 PMID: 1361128
  41. Age-related alterations in the properties of hippocampal pyramidal neurons among rat strains.
    Neurobiol Aging. 1993 Jan-Feb;14(1):17-25 PMID: 8450929
  42. Evidence for multiple types of Ca2+ channels in acutely isolated hippocampal CA3 neurones of the guinea-pig.
    J Physiol. 1991 Feb;433:259-81 PMID: 1668752
  43. Calcium currents in the A7r5 smooth muscle-derived cell line. Increase in current and selective removal of voltage-dependent inactivation by intracellular trypsin.
    J Gen Physiol. 1991 Dec;98(6):1127-40 PMID: 1664456
  44. Molecular properties of calcium channels in skeletal muscle and neurons.
    Ann N Y Acad Sci. 1993 Jun 21;681:342-55 PMID: 8395149
  45. Inactivation kinetics of calcium current of acutely dissociated CA1 pyramidal cells of the mature guinea-pig hippocampus.
    J Physiol. 1991 Jun;437:27-48 PMID: 1653853
  46. Pharmacological basis for the use of nimodipine in central nervous system disorders.
    FASEB J. 1989 May;3(7):1799-806 PMID: 2565839
  47. Normal aging: regionally specific changes in hippocampal synaptic transmission.
    Trends Neurosci. 1994 Jan;17(1):13-8 PMID: 7511843
  48. Low Ba2+ and Ca2+ induce a sustained high probability of repolarization openings of L-type Ca2+ channels in hippocampal neurons: physiological implications.
    Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11792-6 PMID: 7505447
  49. Age-related alterations in potentiation in the CA1 region in F344 rats.
    Neurobiol Aging. 1993 May-Jun;14(3):249-58 PMID: 8321393
  50. Probable Ca2+-mediated inactivation of Ca2+ currents in mammalian brain neurons.
    Brain Res. 1987 Apr 28;410(1):147-53 PMID: 2438012
  51. Diminished calcium currents in aged hippocampal dentate gyrus granule neurones.
    Brain Res. 1989 Feb 13;479(2):384-90 PMID: 2493966
  52. Loss of place specificity in hippocampal complex spike cells of senescent rat.
    Neurobiol Aging. 1983 Summer;4(2):113-9 PMID: 6633780
  53. Optical imaging of calcium accumulation in hippocampal pyramidal cells during synaptic activation.
    Nature. 1989 Oct 12;341(6242):533-6 PMID: 2797180
  54. Voltage-activated calcium channels that must be phosphorylated to respond to membrane depolarization.
    Proc Natl Acad Sci U S A. 1987 Apr;84(8):2518-22 PMID: 2436233
  55. The role of calcium regulation in brain aging: reexamination of a hypothesis.
    Aging (Milano). 1989 Sep;1(1):17-34 PMID: 2488296
  56. Inactivation of Ca channels.
    Prog Biophys Mol Biol. 1984;44(3):215-67 PMID: 6095365
  57. Hippocampal markers of age-related memory dysfunction: behavioral, electrophysiological and morphological perspectives.
    Prog Neurobiol. 1995 Feb;45(3):223-52 PMID: 7777673
  58. Advances in Alzheimer's disease.
    FASEB J. 1991 Mar 1;5(3):278-86 PMID: 2001787
  59. Calcium currents in aged rat dorsal root ganglion neurones.
    J Physiol. 1993 Feb;461:467-83 PMID: 8394426
  60. Functional aspects of calcium-channel modulation.
    Clin Neuropharmacol. 1993;16 Suppl 1:S12-24 PMID: 8390916
  61. Voltage clamp discloses slow inward current in hippocampal burst-firing neurones.
    Nature. 1980 Jul 24;286(5771):391-3 PMID: 7402320
  62. Nimodipine decreases calcium action potentials in rabbit hippocampal CA1 neurons in an age-dependent and concentration-dependent manner.
    Hippocampus. 1994 Feb;4(1):11-7 PMID: 8061749
  63. Nimodipine facilitates associative learning in aging rabbits.
    Science. 1989 Feb 10;243(4892):809-11 PMID: 2916127
  64. Calcium: still center-stage in hypoxic-ischemic neuronal death.
    Trends Neurosci. 1995 Feb;18(2):58-60 PMID: 7537408
  65. Identification and differential subcellular localization of the neuronal class C and class D L-type calcium channel alpha 1 subunits.
    J Cell Biol. 1993 Nov;123(4):949-62 PMID: 8227151
  66. Aging-related prolongation of calcium spike duration in rat hippocampal slice neurons.
    Brain Res. 1990 Jan 29;508(1):1-6 PMID: 2337778
  67. Divalent cation dependent inactivation of the high-voltage-activated Ca-channel current in chick sensory neurons.
    Pflugers Arch. 1988 Jun;411(6):695-7 PMID: 2457872
  68. Blockade of current through single calcium channels by Cd2+, Mg2+, and Ca2+. Voltage and concentration dependence of calcium entry into the pore.
    J Gen Physiol. 1986 Sep;88(3):321-47 PMID: 2428920
  69. Two types of calcium channels in the somatic membrane of new-born rat dorsal root ganglion neurones.
    J Physiol. 1985 Feb;359:431-46 PMID: 2582115
  70. Passive electrical constants in three classes of hippocampal neurons.
    J Neurophysiol. 1981 Oct;46(4):812-27 PMID: 7288466
  71. Mechanisms of neuronal death in brain aging and Alzheimer's disease: role of endocrine-mediated calcium dyshomeostasis.
    J Neurobiol. 1992 Nov;23(9):1247-60 PMID: 1469387
  72. Calcium binding to the cytosol and calcium extrusion mechanisms in intact synaptosomes and their alterations with aging.
    J Biol Chem. 1992 Mar 5;267(7):4672-9 PMID: 1531657
  73. Multiple voltage-dependent mechanisms potentiate calcium channel activity in hippocampal neurons.
    J Neurosci. 1996 Feb 1;16(3):1072-82 PMID: 8558236
  74. Properties and distribution of single voltage-gated calcium channels in adult hippocampal neurons.
    J Neurophysiol. 1990 Jul;64(1):91-104 PMID: 1696962
  75. Low-voltage activated calcium currents increase in basal forebrain neurons from aged rats.
    J Neurophysiol. 1995 Aug;74(2):876-87 PMID: 7472390
  76. Calcium and the aging nervous system.
    Neurobiol Aging. 1987 Jul-Aug;8(4):329-43 PMID: 3306433
  77. Diminished interaction of norepinephrine with climbing fiber inputs to cerebellar Purkinje neurons in aged Fischer 344 rats.
    Brain Res. 1986 Oct 22;385(2):405-10 PMID: 3022875
  78. Hippocampal glucocorticoid receptor activation enhances voltage-dependent Ca2+ conductances: relevance to brain aging.
    Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8527-31 PMID: 1528857
  79. Control of the repetitive discharge of rat CA 1 pyramidal neurones in vitro.
    J Physiol. 1984 Sep;354:319-31 PMID: 6434729
  80. Dendritic attenuation of synaptic potentials and currents: the role of passive membrane properties.
    Trends Neurosci. 1994 Apr;17(4):161-6 PMID: 7517596
  81. Role of calcium channel subtypes in calcium transients in hippocampal CA3 neurons.
    J Neurosci. 1995 Oct;15(10):6433-44 PMID: 7472406
  82. Submicroscopic Ca2+ diffusion mediates inhibitory coupling between individual Ca2+ channels.
    Neuron. 1992 Aug;9(2):197-207 PMID: 1323309
  83. Ca2+ and voltage inactivate Ca2+ channels in guinea-pig ventricular myocytes through independent mechanisms.
    J Physiol. 1991 Dec;444:257-68 PMID: 1668348
Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
0270-6474
Published
1996-10-01
Pages
6286-95
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6579167
Subset
IM
Grants
NIA NIH HHS · P01 AG010836 · United States
NIA NIH HHS · R37 AG004542 · United States
NIA NIH HHS · AG04542 · United States
NIA NIH HHS · AG10836 · United States
External Links
PubMed source PMC Full Text View journal details
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