Kv3 potassium conductance is necessary and kinetically optimized for high-frequency action potential generation in hippocampal interneurons Journal Article


Author(s): Lien, Cheng-Chang; Jonas, Peter
Article Title: Kv3 potassium conductance is necessary and kinetically optimized for high-frequency action potential generation in hippocampal interneurons
Affiliation
Abstract: Kv3 channels are thought to be essential for the fast-spiking (FS) phenotype in GABAergic interneurons, but how these channels confer the ability to generate action potentials (APs) at high frequency is unknown. To address this question, we developed a fast dynamic-clamp system (approximately 50 kHz) that allowed us to add a Kv3 model conductance to CA1 oriens alveus (OA) interneurons in hippocampal slices. Selective pharmacological block of Kv3 channels by 0.3 mm 4-aminopyridine or 1 mm tetraethylammonium ions led to a marked broadening of APs during trains of short stimuli and a reduction in AP frequency during 1 sec stimuli. The addition of artificial Kv3 conductance restored the original AP pattern. Subtraction of Kv3 conductance by dynamic clamp mimicked the effects of the blockers. Application of artificial Kv3 conductance also led to FS in OA interneurons after complete K+ channel block and even induced FS in hippocampal pyramidal neurons in the absence of blockers. Adding artificial Kv3 conductance with altered deactivation kinetics revealed a nonmonotonic relationship between mean AP frequency and deactivation rate, with a maximum slightly above the original value. Insertion of artificial Kv3 conductance with either lowered activation threshold or inactivation also led to a reduction in the mean AP frequency. However, the mechanisms were distinct. Shifting the activation threshold induced adaptation, whereas adding inactivation caused frequency-dependent AP broadening. In conclusion, Kv3 channels are necessary for the FS phenotype of OA interneurons, and several of their gating properties appear to be optimized for high-frequency repetitive activity.
Keywords: Animals; Rats; Phenotype; Kinetics; Electric Stimulation; Models, Neurological; Rats, Wistar; Ion Channel Gating/physiology; Patch-Clamp Techniques/methods; Potassium Channel Blockers/pharmacology; Sensory Thresholds/physiology; Shaw Potassium Channels; Signal Processing, Computer-Assisted; Hippocampus/cytology/physiology; Action Potentials/drug effects/physiology; Interneurons/drug effects/metabolism/physiology; Potassium Channels/drug effects/metabolism; Potassium Channels, Voltage-Gated; Kv3 channels dynamic clamp; fast spiking; deactivation kinetics; OA interneurons; hippocampal slices; two electrode current clamp
Journal Title: Journal of Neuroscience
Volume: 23
Issue 6
ISSN: 1529-2401
Publisher: Society for Neuroscience  
Publication Place: United States
Date Published: 2003-01-01
Start Page: 2058
End Page: 68
Open access: no