Kv3 Potassium Conductance is Necessary and Kinetically Optimized for High-Frequency Action Potential Generation in Hippocampal Interneurons

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.

Sodium Currents Activate without a Hodgkin and Huxley-Type Delay in Central Mammalian Neurons

“…1), such brief delays may be caused at least in part by membrane charging. However, these data do not exclude the existence of a brief delay (see below) similar to what reported for the Kv3 potassium currents (Lien and Jonas, 2003).…”

“…not an experimental artifact (see below) (Lien and Jonas, 2003). Therefore, the peak value of the time constants corresponding to the transition between two closed states was set to be ϳ100 s.…”

Distinct Subtypes of Somatostatin-Containing Neocortical Interneurons Revealed in Transgenic Mice

“…The unusually low input resistance of these cells is likely to be caused by "leak" potassium conductances, such as the two-pore channels formed by the KCNK gene family (Goldstein et al, 2001). Stuttering has been associated with the expression of dendrotoxin-sensitive K v 1.1 potassium channels , and fastspiking properties are thought to depend on the K V 3.X family of potassium channels (Erisir et al, 1999;Lien and Jonas, 2003). The detailed molecular basis for the unique electrophysiological fingerprint of X94 cells remains to be determined.…”

The Role of BKCa Channels in Electrical Signal Encoding in the Mammalian Auditory Periphery

“…Action potential (AP) waveforms and spiking patterns of neurons are shaped by K ϩ channels activated during single spikes or spike trains via depolarization or subsequent elevation of cytoplasmic Ca 2ϩ (Connor and Stevens, 1971;Golding et al, 1999;Lien and Jonas, 2003). In particular, BK Ca channels, which are largeconductance, voltage-and Ca 2ϩ -dependent K ϩ channels, play a prominent role in determining the AP phenotype in many neurons (Vergara et al, 1998;Shao et al, 1999;Faber and Sah, 2003).…”