Neurotransmitter modulation of small-conductance Ca2+-activated K+ channels by regulation of Ca2+ gating.
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.
Maingret
François
F
Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille (CRN2M), CNRS UMR 6231, Université de la Méditerranée, Boulevard Pierre Dramard, 13916, Marseille Cedex 20, France.
Coste
Bertrand
B
Hao
Jizhe
J
Giamarchi
Aurélie
A
Allen
Duane
D
Crest
Marcel
M
Litchfield
David W
DW
Adelman
John P
JP
Delmas
Patrick
P
D000200:Action Potentials; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001345:Autoradiography / Q000379:methods; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000502:physiology; D002147:Calmodulin; D002478:Cells, Cultured; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D008845:Microinjections / Q000379:methods; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D051381:Rats; D015398:Signal Transduction; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*; D017783:Superior Cervical Ganglion / Q000166:cytology
C503279:Cacna1b protein, rat; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D002147:Calmodulin; D004791:Enzyme Inhibitors; D018377:Neurotransmitter Agents; D051640:Small-Conductance Calcium-Activated Potassium Channels; D001030:Apamin; D002118:Calcium