Home LiteratureArticle Details
PMID: 12040053 Published · ppublish English Journal Article

Developmental regulation of small-conductance Ca2+-activated K+ channel expression and function in rat Purkinje neurons.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 22 ·No. 11 ·2002-06-01 ·Pages 4456-67

Cingolani LA, Gymnopoulos M, Boccaccio A, Stocker M, Pedarzani P

Abstract

Calcium transients play an important role in the early and later phases of differentiation and maturation of single neurons and neuronal networks. Small-conductance calcium-activated potassium channels of the SK type modulate membrane excitability and are important determinants of the firing properties of central neurons. Increases in the intracellular calcium concentration activate SK channels, leading to a hyperpolarization of the membrane potential, which in turn reduces the calcium inflow into the cell. This feedback mechanism is ideally suited to regulate the spatiotemporal occurrence of calcium transients. However, the role of SK channels in neuronal development has not been addressed so far. We have concentrated on the ontogenesis and function of SK channels in the developing rat cerebellum, focusing particularly on Purkinje neurons. Electrophysiological recordings combined with specific pharmacological tools have revealed for the first time the presence of an afterhyperpolarizing current (I(AHP)) in immature Purkinje cells in rat cerebellar slices. The channel subunits underlying this current were identified as SK2 and localized by in situ hybridization and subunit-specific antibodies. Their expression level was shown to be high at birth and subsequently to decline during the first 3 weeks of postnatal life, both at the mRNA and protein levels. This developmental regulation was tightly correlated with the expression of I(AHP) and the prominent role of SK2 channels in shaping the spontaneous firing pattern in young, but not in adult, Purkinje neurons. These results provide the first evidence of the developmental regulation and function of SK channels in central neurons.

MeSH Terms
Action Potentials/drug effects,physiology Aging/metabolism Animals Apamin/pharmacology Calcium/pharmacology Calcium Channel Agonists/pharmacology Calcium Signaling/physiology Cell Line Cerebellum/cytology,drug effects,growth & development,metabolism Gene Expression Regulation, Developmental/physiology Humans Immunohistochemistry In Situ Hybridization In Vitro Techniques Kidney/cytology,metabolism Male Membrane Potentials/physiology Patch-Clamp Techniques Potassium Channel Blockers/pharmacology Potassium Channels/genetics,metabolism Potassium Channels, Calcium-Activated Protein Subunits Purkinje Cells/drug effects,metabolism RNA, Messenger/metabolism Rats Rats, Wistar Small-Conductance Calcium-Activated Potassium Channels Tetrodotoxin/pharmacology Transfection
Chemicals
Calcium Channel Agonists KCNN2 protein, human Kcnn2 protein, rat Potassium Channel Blockers Potassium Channels Potassium Channels, Calcium-Activated Protein Subunits RNA, Messenger Small-Conductance Calcium-Activated Potassium Channels Apamin Tetrodotoxin Calcium
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Cingolani Lorenzo A
Max-Planck-Institute for Experimental Medicine, 37075 Göttingen, Germany.
Gymnopoulos Marco
Boccaccio Anna
Stocker Martin
Pedarzani Paola
References (63)
63 references, click to expand
  1. The cells and molecules that make a cerebellum.
    Trends Neurosci. 1998 Sep;21(9):375-82 PMID: 9735945
  2. The histogenesis of the mouse cerebellum as studied by its tritiated thymidine uptake.
    J Comp Neurol. 1960 Apr;114:137-59 PMID: 13840582
  3. An apamin-sensitive Ca2+-activated K+ current in hippocampal pyramidal neurons.
    Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4662-7 PMID: 10200319
  4. Localized calcium signalling and neuronal integration in cerebellar Purkinje neurones.
    Cell Calcium. 1996 Aug;20(2):215-26 PMID: 8889210
  5. Ontogeny of the calcium binding protein parvalbumin in the rat nervous system.
    Anat Embryol (Berl). 1991;184(2):103-24 PMID: 1952098
  6. Developmental changes in human cerebellum: expression of intracellular calcium receptors, calcium-binding proteins, and phosphorylated and nonphosphorylated neurofilament protein.
    J Comp Neurol. 1998 Jul 13;396(4):442-60 PMID: 9651004
  7. Differential expression of three classes of voltage-gated Ca(2+) channels during maturation of the rat cerebellum in vitro.
    Brain Res Dev Brain Res. 1999 Jun 2;115(2):161-70 PMID: 10407133
  8. Ca2+ stores in Purkinje neurons: endoplasmic reticulum subcompartments demonstrated by the heterogeneous distribution of the InsP3 receptor, Ca(2+)-ATPase, and calsequestrin.
    J Neurosci. 1992 Feb;12(2):489-505 PMID: 1311032
  9. Developmental changes in K+-selective channel activity during differentiation of the Purkinje neuron in culture.
    J Neurosci. 1988 Jun;8(6):1971-80 PMID: 2455025
  10. Ionic currents underlying spontaneous action potentials in isolated cerebellar Purkinje neurons.
    J Neurosci. 1999 Mar 1;19(5):1663-74 PMID: 10024353
  11. Distribution of high-conductance Ca(2+)-activated K+ channels in rat brain: targeting to axons and nerve terminals.
    J Neurosci. 1996 Feb 1;16(3):955-63 PMID: 8558264
  12. Supralinear Ca2+ signaling by cooperative and mobile Ca2+ buffering in Purkinje neurons.
    Neuron. 1999 Dec;24(4):989-1002 PMID: 10624961
  13. L-Type calcium channels mediate calcium oscillations in early postnatal Purkinje neurons.
    J Neurosci. 2000 Oct 1;20(19):7394-403 PMID: 11007898
  14. Spatially resolved calcium dynamics of mammalian Purkinje cells in cerebellar slice.
    Science. 1988 Nov 4;242(4879):773-7 PMID: 2847315
  15. Spontaneous activity of cerebellar Purkinje cells and their responses to impulses in climbing fibres.
    J Physiol. 1971 Feb;213(1):135-56 PMID: 5575334
  16. Pharmacological characterization of small-conductance Ca(2+)-activated K(+) channels stably expressed in HEK 293 cells.
    Br J Pharmacol. 2000 Mar;129(5):991-9 PMID: 10696100
  17. Analysis of spontaneous electrical activity in cerebellar Purkinje cells acutely isolated from postnatal rats.
    J Neurobiol. 1997 Jul;33(1):18-32 PMID: 9212067
  18. Calcium signaling in a narrow somatic submembrane shell during synaptic activity in cerebellar Purkinje neurons.
    Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10272-6 PMID: 7479766
  19. Development of electrical excitability in embryonic neurons: mechanisms and roles.
    J Neurobiol. 1998 Oct;37(1):190-7 PMID: 9777741
  20. The neuronal EF-hand calcium-binding protein visinin-like protein-3 is expressed in cerebellar Purkinje cells and shows a calcium-dependent membrane association.
    Neuroscience. 2000;96(1):121-9 PMID: 10683417
  21. Electrophysiological properties of in vitro Purkinje cell dendrites in mammalian cerebellar slices.
    J Physiol. 1980 Aug;305:197-213 PMID: 7441553
  22. Regulation of Ca2+-dependent K+ channel expression in rat cerebellum during postnatal development.
    J Neurosci. 1998 Jan 1;18(1):16-25 PMID: 9412482
  23. Potassium channel toxins.
    Pharmacol Ther. 1990;46(1):137-62 PMID: 2181489
  24. Role of alternative splicing in generating isoform diversity among plasma membrane calcium pumps.
    Physiol Rev. 2001 Jan;81(1):21-50 PMID: 11152753
  25. Developing networks play a similar melody.
    Trends Neurosci. 2001 Jun;24(6):353-60 PMID: 11356508
  26. Regulation of the rebound depolarization and spontaneous firing patterns of deep nuclear neurons in slices of rat cerebellum.
    J Neurophysiol. 1999 Oct;82(4):1697-709 PMID: 10515960
  27. Mechanisms of neural patterning and specification in the developing cerebellum.
    Annu Rev Neurosci. 1995;18:385-408 PMID: 7605067
  28. Dendro-somatic distribution of calcium-mediated electrogenesis in purkinje cells from rat cerebellar slice cultures.
    J Physiol. 2000 Sep 1;527 Pt 2:265-82 PMID: 10970428
  29. Potassium currents modulation of calcium spike firing in dendrites of cerebellar Purkinje cells.
    Exp Brain Res. 1998 Oct;122(3):283-94 PMID: 9808301
  30. Molecular cloning of calmodulin mRNA species which are preferentially expressed in neurons in the rat brain.
    Brain Res Mol Brain Res. 1992 Mar;13(1-2):7-17 PMID: 1315919
  31. The origin of spontaneous activity in developing networks of the vertebrate nervous system.
    Curr Opin Neurobiol. 1999 Feb;9(1):94-104 PMID: 10072366
  32. Differential expression of the small-conductance, calcium-activated potassium channel SK3 is critical for pacemaker control in dopaminergic midbrain neurons.
    J Neurosci. 2001 May 15;21(10):3443-56 PMID: 11331374
  33. Antisense knockdown of calcium-dependent K+ channels in developing cerebellar Purkinje neurons.
    Brain Res Dev Brain Res. 2000 Apr 14;120(2):135-40 PMID: 10775766
  34. Voltage-dependent calcium currents in Purkinje cells from rat cerebellar vermis.
    J Neurosci. 1991 Jul;11(7):2259-69 PMID: 1712382
  35. Developmental changes in calcium conductances contribute to the physiological maturation of cerebellar Purkinje neurons in culture.
    J Neurosci. 1992 Jul;12(7):2838-48 PMID: 1377238
  36. hSK4, a member of a novel subfamily of calcium-activated potassium channels.
    Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):11013-8 PMID: 9380751
  37. Patch-clamp recordings from cerebellar basket cell bodies and their presynaptic terminals reveal an asymmetric distribution of voltage-gated potassium channels.
    J Neurosci. 1998 Feb 1;18(3):948-55 PMID: 9437016
  38. High endogenous calcium buffering in Purkinje cells from rat cerebellar slices.
    J Physiol. 1996 Nov 1;496 ( Pt 3):617-25 PMID: 8930830
  39. Electrophysiological properties of in vitro Purkinje cell somata in mammalian cerebellar slices.
    J Physiol. 1980 Aug;305:171-95 PMID: 7441552
  40. Calcium binding protein (calbindin-D28k) gene expression in the developing and aging mouse cerebellum.
    Brain Res Mol Brain Res. 1990 Oct;8(4):283-90 PMID: 2176707
  41. Small-conductance, calcium-activated potassium channels from mammalian brain.
    Science. 1996 Sep 20;273(5282):1709-14 PMID: 8781233
  42. Resurgent sodium current and action potential formation in dissociated cerebellar Purkinje neurons.
    J Neurosci. 1997 Jun 15;17(12):4517-26 PMID: 9169512
  43. Spontaneous Ca2+ spikes and waves in embryonic neurons: signaling systems for differentiation.
    Trends Neurosci. 1994 Mar;17(3):115-8 PMID: 7515527
  44. Ca(2+)-activated K+ currents in neurones: types, physiological roles and modulation.
    Trends Neurosci. 1996 Apr;19(4):150-4 PMID: 8658599
  45. Postnatal development of electrical and enzyme histochemical activity in Purkinje cells.
    Exp Neurol. 1969 Jan;23(1):120-39 PMID: 5765001
  46. Gating properties of single SK channels in hippocampal CA1 pyramidal neurons.
    Biophys J. 1999 Oct;77(4):1905-13 PMID: 10512811
  47. Modulation by K+ channels of action potential-evoked intracellular Ca2+ concentration rises in rat cerebellar basket cell axons.
    J Physiol. 1999 Oct 1;520 Pt 1:65-78 PMID: 10517801
  48. Single-channel K+ currents recorded from the somatic and dendritic regions of cerebellar Purkinje neurons in culture.
    J Neurosci. 1991 Apr;11(4):1002-15 PMID: 2010802
  49. Mechanism of calcium gating in small-conductance calcium-activated potassium channels.
    Nature. 1998 Oct 1;395(6701):503-7 PMID: 9774106
  50. Differential distribution of three Ca(2+)-activated K(+) channel subunits, SK1, SK2, and SK3, in the adult rat central nervous system.
    Mol Cell Neurosci. 2000 May;15(5):476-93 PMID: 10833304
  51. Postnatal development of the cerebellar cortex in the rat. II. Phases in the maturation of Purkinje cells and of the molecular layer.
    J Comp Neurol. 1972 Aug;145(4):399-463 PMID: 5044254
  52. Action potentials, calcium transients and the control of differentiation of excitable cells.
    Curr Opin Neurobiol. 1994 Feb;4(1):70-7 PMID: 7513567
  53. Calcium-induced calcium release in cerebellar Purkinje cells.
    Neuron. 1994 Mar;12(3):663-73 PMID: 7512352
  54. Increased calcium-dependent K+ channel activity contributes to the maturation of cellular firing patterns in developing cerebellar Purkinje neurons.
    Brain Res Dev Brain Res. 1998 Jun 15;108(1-2):193-203 PMID: 9693796
  55. Morphological and physiological differentiation of Purkinje neurons in cultures of rat cerebellum.
    J Neurosci. 1987 May;7(5):1271-93 PMID: 2437259
  56. Electrophysiological characterization of voltage-gated K(+) currents in cerebellar basket and purkinje cells: Kv1 and Kv3 channel subfamilies are present in basket cell nerve terminals.
    J Neurosci. 2000 Jan 1;20(1):114-22 PMID: 10627587
  57. Calcium-dependent potassium currents in neurons from cat sensorimotor cortex.
    J Neurophysiol. 1992 Jan;67(1):216-26 PMID: 1313080
  58. Apamin interacts with all subtypes of cloned small-conductance Ca2+-activated K+ channels.
    Pflugers Arch. 2001 Jan;441(4):544-50 PMID: 11212219
  59. Potassium currents in developing neurons.
    Ann N Y Acad Sci. 1999 Apr 30;868:399-405 PMID: 10414309
  60. Molecular determinants of Ca2+-dependent K+ channel function in rat dorsal vagal neurones.
    J Physiol. 2000 Sep 1;527 Pt 2:283-90 PMID: 10970429
  61. Calcium transients evoked by climbing fiber and parallel fiber synaptic inputs in guinea pig cerebellar Purkinje neurons.
    J Neurophysiol. 1992 Oct;68(4):1178-89 PMID: 1359027
  62. Calcium conductances in Purkinje cell dendrites: their role in development and integration.
    Prog Brain Res. 1979;51:323-34 PMID: 551484
  63. Control of electrical activity in central neurons by modulating the gating of small conductance Ca2+-activated K+ channels.
    J Biol Chem. 2001 Mar 30;276(13):9762-9 PMID: 11134030
Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
20026415
Published
2002-06-01
Pages
4456-67
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6758803
Subset
IM
Grants
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 20026415 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2