Neuron
Volume 11, Issue 6, December 1993, Pages 1023-1035
Journal home page for Neuron

Article
Pka mediates the effects of monoamine transmitters on the K+ current underlying the slow spike frequency adaptation in hippocampal neurons

https://doi.org/10.1016/0896-6273(93)90216-EGet rights and content

Abstract

The Ca2+-activated K+ current IAHP , which underlies spike frequency adaptation in cortical pyramidal cells, can be modulated by multiple transmitters and probably contributes to state control of the forebrain by ascending monoaminergic fibers. Here, we show that the modulation of this current by norepinephrine, serotonin, and histamine is mediated by protein kinase A in hippocampal CA1 neurons. Two specific protein kinase A inhibitors, Rp-cAMPS and Walsh peptide, suppressed the effects of these transmitters on IAHP and spike frequency adaptation. The effects of the cyclic AMP analog 8CPT-cAMP were also inhibited, whereas muscarinic and metabotropic glutamate receptor agonists had full effect. Intracellular application of protein kinase A catalytic subunit or a phosphatase inhibitor mimicked the effects of monoamines or 8CPT-CAMP. These results demonstrate that monoaminergic modulation of neuronal excitability in the mammalian CNS is mediated by protein phosphorylation.

References (101)

  • J. Farley et al.

    Multiple types of voltage-dependent Ca2+-activated K+ channels of large conductance in rat brain synaptosomal membranes

    Biophys. J.

    (1988)
  • H.L. Haas et al.

    Noradrenaline blocks potassium conductance in rat dentate granule cells in vitro

    Neurosci. Lett.

    (1987)
  • T. Hirayama et al.

    Functional supersensitivity of alpha 1-adrenergic system in spinal ventral horn is due to absence of an uptake system and not to postsynaptic change

    Brain Res.

    (1991)
  • J.H. Hoger et al.

    Modulation of a cloned mouse brain potassium channel

    Neuron

    (1991)
  • G.Y. Hu et al.

    Excitatory amino acids acting on metabotropic glutamate receptors broaden the action potential in hippocampal neurons

    Brain Res.

    (1991)
  • C. MacKintosh et al.

    Cyanobacterial microcystin-LR is a potent and specific inhibitor of protein phosphatases 1 and 2A from both mammals and higher plants

    FEBS Lett.

    (1990)
  • D.A. McCormick

    Cholinergic and noradrenergic modulation of thalamocortical processing

    Trends Neurosci.

    (1989)
  • H. Pollard et al.

    Histamine neuronal pathways and their functions

    Trends Neurosci.

    (1987)
  • S.G. Rane et al.

    Specific inhibitors of protein kinase C block transmitter-induced modulation of sensory neuron calcium current

    Neuron

    (1989)
  • L.A. Raymond et al.

    Phosphorylation of amino acid neurotransmitter receptors in synaptic plasticity

    Trends Neurosci.

    (1993)
  • U.T. Rüegg et al.

    Staurosporine, K-252 and UCN-01: potent but nonspecific inhibitors of protein kinases

    Trends Pharmacol. Sci.

    (1989)
  • J.B. Shabb et al.

    Cyclic nucleotide-binding domains in proteins having diverse functions

    J. Biol. Chem.

    (1992)
  • J.F. Storm

    Phorbol esters broaden the action potential in CA1 hippocampal pyramidal cells

    Neurosci. Lett.

    (1987)
  • K.R. Stratton et al.

    Excitation of hippocampal neurons by stimulation of glutamate Qp receptors

    Eur. J. Pharmacol.

    (1989)
  • O.K. Vintermyr et al.

    Microinjected catalytic subunit of cAMP-dependent protein kinase induces apoptosis in myeloid leukemia (IPC-81) cells

    Exp. Cell Res.

    (1993)
  • T. Watanabe et al.

    Evidence for the presence of a histaminergic neuron system in the rat brain: an immunohistochemical analysis

    Neurosci. Lett.

    (1983)
  • W.B. Adams et al.

    Intracellular injection of protein kinase inhibitor blocks the serotonin-induced increase in K+ conductance in Aplysia neuron R15

  • B.E. Alger et al.

    Epileptiform burst after hyperpolarization: calcium-dependent potassium potential in hippocampal CA1 pyramidal cells

    Science

    (1980)
  • R. Andrade et al.

    5-Hydroxytryptamine4-like receptors mediate the slow excitatory response to serotonin in the rat hippocampus

    J. Pharmacol. Exp. Ther.

    (1991)
  • R. Andrade et al.

    Pharmacologically distinct actions of serotonin on single pyramidal neurones of the rat hippocampus recorded in vitro

    J. Physiol.

    (1987)
  • G. Aston-Jones et al.

    Norepinephrine-containing locus coeruleus neurons in behaving rats exhibit pronounced responses to non-noxious environmental stimuli

    J. Neurosci.

    (1981)
  • E.C. Azmitia

    The CNS serotoninergic system: progression toward a collaborative organization

  • M.L. Barbaccia et al.

    Serotonin-elicited amplification of adenylate cyclase activity in hippocampal membranes from adult rat

    J. Neurochem.

    (1983)
  • L. Boland et al.

    Inhibition by bradykinin of voltage-activated barium current in a rat dorsal root ganglion cell line: role of protein kinase C

    J. Neurosci.

    (1991)
  • L.H. Botelho et al.

    CAMP analog antagonists of CAMP action

    Meth. Enzymol.

    (1988)
  • G. Brum et al.

    Injection of catalytic subunit of cAMP-dependent kinase into isolated cardiac myocytes

    Pflügers Arch.

    (1983)
  • V.F. Castellucci et al.

    Intracellular injection of the catalytic subunit of cyclic AMP-dependent protein kinase simulates facilitation of transmitter release underlying behavioral sensitization in Aplysia

  • W.A. Catterall

    Cellular and molecular biology of voltagegated sodium channels

    Physiol. Rev.

    (1992)
  • S. Charpak et al.

    Potassium conductances in hippocampal neurons blocked by excitatory amino acid transmitters

    Nature

    (1990)
  • N. Chu et al.

    Norepinephrine-containing neurons: changes in spontaneous discharge patterns during sleep and waking

    Science

    (1973)
  • S.K. Chung et al.

    Protein kinase activity closely associated with a reconstituted calcium-activated potassium channel

    Science

    (1991)
  • A.E. Cole et al.

    Acetylcholine mediates a slow synaptic potential in hippocampal pyramidal cells

    Science

    (1983)
  • A. Colino et al.

    Differential modulation of three separate K-conductances in hippocampal CA1 neurons by serotonin

    Nature

    (1987)
  • A. Constanti et al.

    Calcium-dependent potassium conductance in guinea-pig olfactory cortex neurones in vitro

    J. Physiol.

    (1987)
  • R. Delgado et al.

    A cyclic AMP-activated K+ channel in Drosophila larval muscle is persistently activated in dunce

    Proc. Natl. Acad. Sci. USA

    (1991)
  • S.A. DeRiemer et al.

    Phorbol ester and protein kinase C enhance calcium current in Aplysia neurones

    Nature

    (1985)
  • D. DiFrancesco et al.

    Direct activation of cardiac pacemaker channels by intracellular cyclic AMP

    Nature

    (1991)
  • A. Dumuis et al.

    A nonclassical 5-hydroxytryptamine receptor positively coupled with adenylate cyclase in the central nervous system

    Mol. Pharmacol.

    (1988)
  • F.A. Edwards et al.

    A thin slice preparation for patch clamp recordings from neurones of the mammalian central nervous system

    Pflügers Arch.

    (1989)
  • E.E. Fesenko et al.

    Induction by cyclic AMP of cationic conductance in plasma membrane of retinal rod outer segment

    Nature

    (1985)
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