NYMC Faculty Publications

Document Type

Article

Publication Date

5-25-2005

Department

Physiology

Abstract

Potassium (K+) channel subunits of the Kv3 subfamily (Kv3.1-Kv3.4) display a positively shifted voltage dependence of activation and fast activation/deactivation kinetics when compared with other voltage-gated K+ channels, features that confer on Kv3 channels the ability to accelerate the repolarization of the action potential (AP) efficiently and specifically. In the cortex, the Kv3.1 and Kv3.2 proteins are expressed prominently in a subset of GABAergic interneurons known as fast-spiking (FS) cells and in fact are a significant determinant of the fast-spiking discharge pattern. However, in addition to expression at FS cell somata, Kv3.1 and Kv3.2 proteins also are expressed prominently at FS cell terminals, suggesting roles for Kv3 channels in neurotransmitter release. We investigated the effect of 1.0 mM tetraethylammonium (TEA; which blocks Kv3 channels) on inhibitory synaptic currents recorded in layer II/III neocortical pyramidal cells. Spike-evoked GABA release by FS cells was enhanced nearly twofold by 1.0 mM TEA, with a decrease in the paired pulse ratio (PPR), effects not reproduced by blockade of the non-Kv3 subfamily K+ channels also blocked by low concentrations of TEA. Moreover, in Kv3.1/Kv3.2 double knock-out (DKO) mice, the large effects of TEA were absent, spike-evoked GABA release was larger, and the PPR was lower than in wild-type mice. Together, these results suggest specific roles for Kv3 channels at FS cell terminals that are distinct from those of Kv1 and large-conductance Ca2+-activated K+ channels (also present at the FS cell synapse). We propose that at FS cell terminals synaptically localized Kv3 channels keep APs brief, limiting Ca2+ influx and hence release probability, thereby influencing synaptic depression at a synapse designed for sustained high-frequency synaptic transmission.

Publisher's Statement

Originally published in The Journal of Neuroscience. Licensed under CC-BY 4.0. https://doi.org/10.1523/JNEUROSCI.0722-05.2005

Share

COinS