TY - JOUR
T1 - The sodium channel accessory subunit Navβ1 regulates neuronal excitability through modulation of repolarizing Voltage-gated K+ channels
AU - Marionneau, Céline
AU - Carrasquillo, Yarimar
AU - Norris, Aaron J.
AU - Reid Townsend, R.
AU - Isom, Lori L.
AU - Link, Andrew J.
AU - Nerbonne, Jeanne M.
PY - 2012/4/25
Y1 - 2012/4/25
N2 - The channel pore-forming α subunit Kv4.2 is a major constituent of A-type (IA) potassium currents and a key regulator of neuronal membraneexcitability. Multiple mechanisms regulate the properties, subcellular targeting, and cell-surface expression of Kv4.2-encoded channels. In the present study, shotgun proteomic analyses of immunoprecipitated mouse brain Kv4.2 channel complexes unexpectedly identified the voltage-gated Na+ channel accessory subunit Navβ1. Voltage-clamp and current-clamp recordings revealed that knockdown of Navβ1 decreases IA densities in isolated cortical neurons and that action potential waveforms are prolonged and repetitive firing is increased in Scn1b-null cortical pyramidal neurons lacking Navβ1. Biochemical and voltage-clamp experiments further demonstrated that Navβ1 interacts with and increases the stability of the heterologously expressed Kv4.2 protein, resulting in greater total and cell-surface Kv4.2 protein expression and in larger Kv4.2-encoded current densities. Together, the results presented here identify Navβ1 as a component of native neuronal Kv4.2-encoded IA channel complexes and a novel regulator of IA channel densities and neuronal excitability.
AB - The channel pore-forming α subunit Kv4.2 is a major constituent of A-type (IA) potassium currents and a key regulator of neuronal membraneexcitability. Multiple mechanisms regulate the properties, subcellular targeting, and cell-surface expression of Kv4.2-encoded channels. In the present study, shotgun proteomic analyses of immunoprecipitated mouse brain Kv4.2 channel complexes unexpectedly identified the voltage-gated Na+ channel accessory subunit Navβ1. Voltage-clamp and current-clamp recordings revealed that knockdown of Navβ1 decreases IA densities in isolated cortical neurons and that action potential waveforms are prolonged and repetitive firing is increased in Scn1b-null cortical pyramidal neurons lacking Navβ1. Biochemical and voltage-clamp experiments further demonstrated that Navβ1 interacts with and increases the stability of the heterologously expressed Kv4.2 protein, resulting in greater total and cell-surface Kv4.2 protein expression and in larger Kv4.2-encoded current densities. Together, the results presented here identify Navβ1 as a component of native neuronal Kv4.2-encoded IA channel complexes and a novel regulator of IA channel densities and neuronal excitability.
UR - http://www.scopus.com/inward/record.url?scp=84860139400&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.6450-11.2012
DO - 10.1523/JNEUROSCI.6450-11.2012
M3 - Article
C2 - 22539834
AN - SCOPUS:84860139400
SN - 0270-6474
VL - 32
SP - 5716
EP - 5727
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 17
ER -