K+ channels at the axon initial segment dampen near-threshold excitability of neocortical fast-spiking GABAergic interneurons.
Fast-spiking cells (FS cells) are a prominent subtype of neocortical GABAergic interneurons with important functional roles. Multiple FS cell properties are coordinated for rapid response. Here, we describe an FS cell feature that serves to gate the powerful inhibition produced by FS cell activity. We show that FS cells in layer 2/3 barrel cortex possess a dampening mechanism mediated by Kv1.1-containing potassium channels localized to the axon initial segment. These channels powerfully regulate action potential threshold and allow FS cells to respond preferentially to large inputs that are fast enough to "outrun" Kv1 activation. In addition, Kv1.1 channel blockade converts the delay-type discharge pattern of FS cells to one of continuous fast spiking without influencing the high-frequency firing that defines FS cells. Thus, Kv1 channels provide a key counterbalance to the established rapid-response characteristics of FS cells, regulating excitability through a unique combination of electrophysiological properties and discrete subcellular localization.
Goldberg
Ethan M
EM
Smilow Neuroscience Program, New York University School of Medicine, Smilow Research Building, Sixth Floor, 522 First Avenue, New York, NY 10016, USA.
Clark
Brian D
BD
Zagha
Edward
E
Nahmani
Mark
M
Erisir
Alev
A
Rudy
Bernardo
B
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000502:physiology*; D003198:Computer Simulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D007395:Interneurons / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D019579:Neocortex / Q000166:cytology / Q000502:physiology; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D051637:Shaker Superfamily of Potassium Channels / Q000502:physiology*; D013003:Somatosensory Cortex / Q000166:cytology / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D051637:Shaker Superfamily of Potassium Channels; D049452:Green Fluorescent Proteins; D005680:gamma-Aminobutyric Acid