Channelpedia

PubMed 18701069


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: KCNQ2 , Kv7.2 , SK2



Title: Neurotransmitter modulation of small-conductance Ca2+-activated K+ channels by regulation of Ca2+ gating.

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

Journal, date & volume: Neuron, 2008 Aug 14 , 59, 439-49

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/18701069


Abstract
Small-conductance Ca2+-activated K+ (SK) channels are widely expressed in neuronal tissues where they underlie post-spike 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 involvesSK2-associated CK2 and results from a 3-fold reduction in the Ca2+ sensitivity of channel gating. CK2phosphorylated 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 aCK2-dependent fashion. Hence, neurotransmitter-initiated signaling cascades can dynamically regulate Ca2+ sensitivity of SK channels and directly influence somatic excitability.