Voltage-Gated Potassium Channel Kv3.1b is Regulated by the Sodium Channel Beta3 Subunit

Abstract

Voltage-gated K+ Kv3.1b channel has a crucial role in regulating the highfrequency firing properties of neurons and is abundantly expressed in the proximal dendrites, the somatodendritic region, and the axonal nodes of Ranvier. Here we unexpectedly identified Navβ3, an auxiliary subunit of Nav channels, as an integral part of the Kv3.1b channel complex in rat brain using mass spectrometry. Navβ3 reduces the stability of the heterologously expressed Kv3.1b proteins. Interestingly, we found the differences of Kv3.1b and Navβ3 expression between distinct regions of the brain. Kv3.1b protein is highly expressed in cerebellum and brainstem, whereas Navβ3 is expressed in cerebrum and brain stem. This shows an age-dependent pattern in rat brain. Navβ3 significantly decreases the current densities of Kv3.1b in a voltage-dependent manner and alters in the voltage dependence of its steady-state inactivation. In conclusion, our data indicate Navβ3 as a component of neuronal Kv3.1b channel complexes and a functional modulator for Kv3.1b.