Neurotransmitter Modulation of Small-Conductance Ca2+-Activated K+ Channels by Regulation of Ca2+ Gating

François Maingret, Bertrand Coste, Jizhe Hao, Aurélie Giamarchi, Duane Allen, Marcel Crest, David W. Litchfield, John P. Adelman, Patrick Delmas

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Small-conductance Ca2+-activated K+ (SK) channels are widely expressed in neuronal tissues where they underlie postspike hyperpolarizations, regulate spike-frequency adaptation, and shape synaptic responses. SK channels constitutively interact with calmodulin (CaM), which serves as Ca2+ sensor, and with protein kinase CK2 and protein phosphatase 2A, which modulate their Ca2+ gating. By recording coupled activities of Ca2+ and SK2 channels, we showed that SK2 channels can be inhibited by neurotransmitters independently of changes in the activity of the priming Ca2+ channels. This inhibition involves SK2-associated CK2 and results from a 3-fold reduction in the Ca2+ sensitivity of channel gating. CK2 phosphorylated SK2-bound CaM but not KCNQ2-bound CaM, thereby selectively regulating SK2 channels. We extended these observations to sensory neurons by showing that noradrenaline inhibits SK current and increases neuronal excitability in a CK2-dependent fashion. Hence, neurotransmitter-initiated signaling cascades can dynamically regulate Ca2+ sensitivity of SK channels and directly influence somatic excitability.

Original languageEnglish (US)
Pages (from-to)439-449
Number of pages11
JournalNeuron
Volume59
Issue number3
DOIs
StatePublished - Aug 14 2008

Keywords

  • MOLNEURO
  • PROTEINS

ASJC Scopus subject areas

  • Neuroscience(all)

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