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PMID: 10516298 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Dendritic calcium spike initiation and repolarization are controlled by distinct potassium channel subtypes in CA1 pyramidal neurons.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 19 ·No. 20 ·1999-10-15 ·Pages 8789-98

Golding NL, Jung HY, Mickus T, Spruston N

Abstract

In CA1 pyramidal neurons of the hippocampus, calcium-dependent spikes occur in vivo during specific behavioral states and may be enhanced during epileptiform activity. However, the mechanisms that control calcium spike initiation and repolarization are poorly understood. Using dendritic and somatic patch-pipette recordings, we show that calcium spikes are initiated in the apical dendrites of CA1 pyramidal neurons and drive bursts of sodium-dependent action potentials at the soma. Initiation of calcium spikes at the soma was suppressed in part by potassium channels activated by sodium-dependent action potentials. Low-threshold, putative D-type potassium channels [blocked by 100 microM 4-aminopyridine (4-AP) and 0.5-1 microM alpha-dendrotoxin (alpha-DTX)] played a prominent role in setting a high threshold for somatic calcium spikes, thus restricting initiation to the dendrites. DTX- and 4-AP-sensitive channels were activated during sodium-dependent action potentials and mediated a large component of their afterhyperpolarization. Once initiated, repetitive firing of calcium spikes was limited by activation of putative BK-type calcium-activated potassium channels (blocked by 250 microM tetraethylammonium chloride, 70 nM charybdotoxin, or 100 nM iberiotoxin). Thus, the concerted action of calcium- and voltage-activated potassium channels serves to focus spatially and temporally the membrane depolarization and calcium influx generated by calcium spikes during strong, synchronous network excitation.

MeSH Terms
4-Aminopyridine/pharmacology Action Potentials Animals Calcium/physiology Dendrites/physiology Elapid Venoms/pharmacology Electrophysiology Hippocampus/cytology,physiology Large-Conductance Calcium-Activated Potassium Channels Male Potassium Channel Blockers Potassium Channels/physiology Potassium Channels, Calcium-Activated Protein Isoforms/physiology Pyramidal Cells/physiology Rats Rats, Wistar Sodium/physiology Tetraethylammonium/pharmacology
Chemicals
Elapid Venoms Large-Conductance Calcium-Activated Potassium Channels Potassium Channel Blockers Potassium Channels Potassium Channels, Calcium-Activated Protein Isoforms Tetraethylammonium dendrotoxin Sodium 4-Aminopyridine Calcium
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Golding N L
Department of Neurobiology and Physiology, Institute for Neuroscience, Northwestern University, Evanston, Illinois 60208, USA.
Jung H Y
Mickus T
Spruston N
References (53)
53 references, click to expand
  1. Central action of dendrotoxin: selective reduction of a transient K conductance in hippocampus and binding to localized acceptors.
    Proc Natl Acad Sci U S A. 1986 Jan;83(2):493-7 PMID: 2417246
  2. Amplification of EPSPs by axosomatic sodium channels in neocortical pyramidal neurons.
    Neuron. 1995 Nov;15(5):1065-76 PMID: 7576650
  3. Whole-cell recording of the Ca(2+)-dependent slow afterhyperpolarization in hippocampal neurones: effects of internally applied anions.
    Pflugers Arch. 1994 Feb;426(3-4):247-53 PMID: 8183635
  4. Biochemical properties and subcellular distribution of an N-type calcium channel alpha 1 subunit.
    Neuron. 1992 Dec;9(6):1099-115 PMID: 1334419
  5. Differential distribution of three members of a gene family encoding low voltage-activated (T-type) calcium channels.
    J Neurosci. 1999 Mar 15;19(6):1895-911 PMID: 10066243
  6. Hippocampal pyramidal cells: significance of dendritic ionic conductances for neuronal function and epileptogenesis.
    J Neurophysiol. 1979 Mar;42(2):476-96 PMID: 422974
  7. Regenerative properties of pyramidal cell dendrites in area CA1 of the rat hippocampus.
    J Physiol. 1995 Mar 1;483 ( Pt 2):421-41 PMID: 7650611
  8. Dendritic Na+ channels amplify EPSPs in hippocampal CA1 pyramidal cells.
    J Neurophysiol. 1996 Oct;76(4):2181-91 PMID: 8899593
  9. Properties of two calcium-activated hyperpolarizations in rat hippocampal neurones.
    J Physiol. 1987 Aug;389:187-203 PMID: 2445972
  10. Mechanisms underlying epileptiform burst discharge.
    Ann Neurol. 1980 Feb;7(2):95-107 PMID: 6245619
  11. Patch-clamp recordings from the soma and dendrites of neurons in brain slices using infrared video microscopy.
    Pflugers Arch. 1993 Jun;423(5-6):511-8 PMID: 8351200
  12. Localization of P-type calcium channels in the central nervous system.
    Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7076-80 PMID: 1651493
  13. Action potential initiation and propagation in rat neocortical pyramidal neurons.
    J Physiol. 1997 Dec 15;505 ( Pt 3):617-32 PMID: 9457640
  14. Charybdotoxin, a protein inhibitor of single Ca2+-activated K+ channels from mammalian skeletal muscle.
    Nature. 1985 Jan 24-30;313(6000):316-8 PMID: 2578618
  15. Probable calcium spikes in hippocampal neurons.
    Brain Res. 1977 Oct 21;135(1):157-61 PMID: 912429
  16. Pattern and inhibition-dependent invasion of pyramidal cell dendrites by fast spikes in the hippocampus in vivo.
    Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9921-5 PMID: 8790432
  17. Properties of calcium spikes revealed during GABAA receptor antagonism in hippocampal CA1 neurons from guinea pigs.
    J Neurophysiol. 1997 Nov;78(5):2269-79 PMID: 9356380
  18. Dendritic sodium spikes are variable triggers of axonal action potentials in hippocampal CA1 pyramidal neurons.
    Neuron. 1998 Nov;21(5):1189-200 PMID: 9856473
  19. Ionic basis of spike after-depolarization and burst generation in adult rat hippocampal CA1 pyramidal cells.
    J Physiol. 1996 Apr 1;492 ( Pt 1):211-23 PMID: 8730596
  20. Cellular bases of hippocampal EEG in the behaving rat.
    Brain Res. 1983 Oct;287(2):139-71 PMID: 6357356
  21. Intradendritic recordings from hippocampal neurons.
    Proc Natl Acad Sci U S A. 1979 Feb;76(2):986-90 PMID: 284423
  22. K+ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons.
    Nature. 1997 Jun 26;387(6636):869-75 PMID: 9202119
  23. Novel effects of dendrotoxin homologues on subtypes of mammalian Kv1 potassium channels expressed in Xenopus oocytes.
    FEBS Lett. 1996 Mar 25;383(1-2):26-30 PMID: 8612784
  24. Cerebellar complex spikes encode both destinations and errors in arm movements.
    Nature. 1998 Apr 2;392(6675):494-7 PMID: 9548253
  25. Different firing patterns generated in dendrites and somata of CA1 pyramidal neurones in guinea-pig hippocampus.
    J Physiol. 1992 Nov;457:675-87 PMID: 1297848
  26. Two pharmacologically and kinetically distinct transient potassium currents in cultured embryonic mouse hippocampal neurons.
    J Neurosci. 1992 Jun;12(6):2235-46 PMID: 1607938
  27. Studies on single neurons in dorsal hippocampal formation and septum in unrestrained rats. I. Behavioral correlates and firing repertoires.
    Exp Neurol. 1973 Nov;41(2):461-531 PMID: 4355646
  28. Action potential initiation and backpropagation in neurons of the mammalian CNS.
    Trends Neurosci. 1997 Mar;20(3):125-31 PMID: 9061867
  29. Spike after-depolarization and burst generation in adult rat hippocampal CA1 pyramidal cells.
    J Physiol. 1996 Apr 1;492 ( Pt 1):199-210 PMID: 8730595
  30. Bursts as a unit of neural information: making unreliable synapses reliable.
    Trends Neurosci. 1997 Jan;20(1):38-43 PMID: 9004418
  31. Activity-dependent action potential invasion and calcium influx into hippocampal CA1 dendrites.
    Science. 1995 Apr 14;268(5208):297-300 PMID: 7716524
  32. Action potential repolarization and a fast after-hyperpolarization in rat hippocampal pyramidal cells.
    J Physiol. 1987 Apr;385:733-59 PMID: 2443676
  33. Calcium-activated potassium conductances contribute to action potential repolarization at the soma but not the dendrites of hippocampal CA1 pyramidal neurons.
    J Neurosci. 1999 Jul 1;19(13):5205-12 PMID: 10377332
  34. Clustering of L-type Ca2+ channels at the base of major dendrites in hippocampal pyramidal neurons.
    Nature. 1990 Sep 20;347(6290):281-4 PMID: 2169591
  35. Regenerative activity in apical dendrites of pyramidal cells in neocortex.
    Cereb Cortex. 1993 Jan-Feb;3(1):26-38 PMID: 8439739
  36. Subthreshold synaptic activation of voltage-gated Ca2+ channels mediates a localized Ca2+ influx into the dendrites of hippocampal pyramidal neurons.
    J Neurophysiol. 1995 Sep;74(3):1335-42 PMID: 7500154
  37. Dendritic spikes are enhanced by cooperative network activity in the intact hippocampus.
    J Neurosci. 1998 May 15;18(10):3919-28 PMID: 9570819
  38. Electrophysiology of isolated hippocampal pyramidal dendrites.
    J Neurosci. 1982 Nov;2(11):1614-22 PMID: 6292377
  39. Ca(2+)-activated K+ currents in neurones: types, physiological roles and modulation.
    Trends Neurosci. 1996 Apr;19(4):150-4 PMID: 8658599
  40. Contributions of voltage-gated Ca2+ channels in the proximal versus distal dendrites to synaptic integration in prefrontal cortical neurons.
    J Neurosci. 1997 Aug 1;17(15):5936-48 PMID: 9221790
  41. Linear summation of excitatory inputs by CA1 pyramidal neurons.
    Neuron. 1999 Feb;22(2):383-94 PMID: 10069343
  42. Calcium action potentials restricted to distal apical dendrites of rat neocortical pyramidal neurons.
    J Physiol. 1997 Dec 15;505 ( Pt 3):605-16 PMID: 9457639
  43. Amplification of EPSPs by low Ni(2+)- and amiloride-sensitive Ca2+ channels in apical dendrites of rat CA1 pyramidal neurons.
    J Neurophysiol. 1997 Mar;77(3):1639-43 PMID: 9084628
  44. Intrinsic firing patterns and whisker-evoked synaptic responses of neurons in the rat barrel cortex.
    J Neurophysiol. 1999 Mar;81(3):1171-83 PMID: 10085344
  45. Frequency-dependent propagation of sodium action potentials in dendrites of hippocampal CA1 pyramidal neurons.
    J Neurophysiol. 1995 Oct;74(4):1395-403 PMID: 8989380
  46. Characterization of single voltage-gated Na+ and Ca2+ channels in apical dendrites of rat CA1 pyramidal neurons.
    J Physiol. 1995 Aug 15;487(1):67-90 PMID: 7473260
  47. Amplification of perforant-path EPSPs in CA3 pyramidal cells by LVA calcium and sodium channels.
    J Neurophysiol. 1998 Sep;80(3):1558-61 PMID: 9744960
  48. Mode of action of iberiotoxin, a potent blocker of the large conductance Ca(2+)-activated K+ channel.
    Biophys J. 1992 Aug;63(2):583-90 PMID: 1384740
  49. Sharp wave-associated high-frequency oscillation (200 Hz) in the intact hippocampus: network and intracellular mechanisms.
    J Neurosci. 1995 Jan;15(1 Pt 1):30-46 PMID: 7823136
  50. The site for initiation of action potential discharge over the somatodendritic axis of rat hippocampal CA1 pyramidal neurons.
    J Neurosci. 1991 Jul;11(7):2270-80 PMID: 2066782
  51. Pharmacological characterization of five cloned voltage-gated K+ channels, types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines.
    Mol Pharmacol. 1994 Jun;45(6):1227-34 PMID: 7517498
  52. Nickel block of a family of neuronal calcium channels: subtype- and subunit-dependent action at multiple sites.
    J Membr Biol. 1996 May;151(1):77-90 PMID: 8661496
  53. Temporal integration by a slowly inactivating K+ current in hippocampal neurons.
    Nature. 1988 Nov 24;336(6197):379-81 PMID: 3194020
Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
1999-10-15
Pages
8789-98
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6782757
Subset
IM
Grants
NINDS NIH HHS · NS-35180 · United States
External Links
PubMed source PMC Full Text View journal details
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