Neuron
Volume 10, Issue 5, May 1993, Pages 889-898
Journal home page for Neuron

GABAB Receptor Inhibition of P-type Ca2+ Channels in Central Neurons

https://doi.org/10.1016/0896-6273(93)90204-5Get rights and content

P-type Ca2+ channels in cerebellar Purkinje neurons were inhibited by GABA and the GABAB receptor agonist baclofen. Inhibition of P-type Ca2+ channel current involved changes in voltage dependence and kinetics. Baclofen induced a slow phase of activation and altered tail current kinetics, and inhibition could be partly overcome by large depolarizations. These effects were mimicked by internal application of GTPyS, which also made the action of baclofen irreversible. In spinal cord neurons, use of selective channel blockers showed that baclofen inhibited both P-type and N-type Ca2+ channels, but not L-type Ca2+ channels; a high threshold current resistant to blockers of P-type, N-type, and L-type channels was also modulated by baclofen. These results show that stimulation of GABAB receptors in central neurons can modulate P-type Ca2+ channels through a G protein-mediated mechanism similar to the one linked to N-type Ca2+ channels.

References (72)

  • LesterR.A.J. et al.

    Quisqualate receptor-mediated depression of calcium currents in hippocampal neurons

    Neuron

    (1990)
  • LlinásR. et al.

    Distribution and functional significance of the P-type, voltage-dependent Ca2+ channels in the mammalian central nervous system

    Trends Neurosci

    (1992)
  • LopezH.S. et al.

    Correlation between G protein activation and reblocking kinetics of Ca2+ channel currents in rat sensory neurons

    Neuron

    (1991)
  • MarchettiC. et al.

    Guanosine 5′-O-(3-triphosphate) modifies kinetics of voltage-dependent Ca2+ current in chick sensory neurons

    Biophys. J.

    (1989)
  • MathieA. et al.

    Inhibition of N- and L-type calcium channels by muscarinic receptor activation in rat sympathetic neurons

    Neuron

    (1992)
  • MillerR.J.

    Voltage-sensitive Ca2+ channels

    J. Biol. Chem.

    (1992)
  • MintzI.M. et al.

    P-type calcium channels in rat central and peripheral neurons

    Neuron

    (1992)
  • SchroederJ.E. et al.

    Activation of p, opioids receptors inhibits transient high- and low-threshold Ca~ currents, but spares a sustained current

    Neuron

    (1991)
  • ScottR.H. et al.

    Modulation of neuronal T-type Ca2+ channels by photoinactivation of intracellular guanosine 5-O-(3-thio) trisphosphate

    Neuroscience

    (1990)
  • ShapiroM.S. et al.

    Substance P and somatostatin inhibit calcium channels in rat sympathetic neurons via different G protein pathways

    Neuron

    (1993)
  • SherE. et al.

    ω-Conotoxin-sensitive voltage-operated calcium channels in vertebrate cells

    Neuroscience

    (1991)
  • SnutchT.P. et al.

    Ca2+ channels: diversity of form and function

    Curr. Opin. Neurobiol.

    (1992)
  • SwandullaD. et al.

    Do calcium channel classifications account for neuronal calcium channel diversity?

    Trends Neurosci

    (1991)
  • TsienR.W. et al.

    Molecular diversity of voltage-dependent Ca2+ channels

    Trends Pharmacol. Sci.

    (1991)
  • UsowiczM.M. et al.

    P-type calcium channels in the somata and dendrites of adult cerebellar Purkinje cells

    Neuron

    (1992)
  • WilliamsM.E. et al.

    Structure and functional expression of α1, α2, and β subunits of a novel human neuronal calcium channel subtype

    Neuron

    (1992)
  • BeanB.P.

    Classes of Ca2+ channels in vertebrate cells

    Annu. Rev. Physiol.

    (1989)
  • BeanB.P.

    Neurotransmitter inhibition of neuronal Ca2+ currents by changes in channel voltage dependence

    Nature

    (1989)
  • BolandL.M. et al.

    Modulation of N-type Ca2+channels in bullfrog sympathetic neurons by luteinizing hormone releasing hormone: kinetics and voltage dependence

    J. Neurosci.

    (1993)
  • BrownA.M. et al.

    Ionic channels and their regulation by G protein subunits

    Annu. Rev. Physiol.

    (1990)
  • CarboneE. et al.

    Neuronal calcium channels: kinetics, blockade and modulation

    Prog. Biophys. Mol. Biol.

    (1989)
  • CoxD.H. et al.

    Pharmacological discrimination of N-type from L-type Ca2+ current and its selective modulation by transmitters

    J. Neurosci.

    (1992)
  • DeiszD.A. et al.

    °-Aminobutyric acid induced depression of Ca2+ currents of chick sensory neurons

    Neurosci. Lett.

    (1985)
  • DolphinA.C. et al.

    Ca2+ channel currents and their inhibition by (-) baclofen in rat sensory neurons: modulation by guanine nucleotides

    J. Physiol.

    (1987)
  • DubelS.J. et al.

    Molecular cloning of the α-1 subunit of an ω-conotoxin Ca2+ channel

  • FisherR. et al.

    Differential modulation of single voltage-gated Ca2+ channels by cholinergic and adrenergic agonists in adult hippocampal neurons

    J. Neurophysiol.

    (1990)
  • Cited by (235)

    • GAD1-mediated GABA elicits aggressive characteristics of human oral cancer cells

      2023, Biochemical and Biophysical Research Communications
    • Ion Channels

      2018, Comprehensive Toxicology: Third Edition
    View all citing articles on Scopus
    View full text