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Accueil > Bibliographie > Neurotransmitter modulation of small-conductance Ca2+-activated K+ channels (...)

Neurotransmitter modulation of small-conductance (...)

Neuron. 2008 Aug ;59(3):439-49
Neurotransmitter modulation of small-conductance Ca2+-activated K+ channels by regulation of Ca2+ gating.
Maingret F, Coste B, Hao J, Giamarchi A, Allen D, Crest M, Litchfield DW, Adelman JP, Delmas P.

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.


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