Key result
Navβ1 interacts with Kv4.2 to increase IA channel densities, and loss of Navβ1 prolongs action potentials and increases repetitive firing in cortical pyramidal neurons.
p-value: p=<0.01
The sodium channel accessory subunit Navβ1 interacts with Kv4.2 to regulate A-type potassium currents and neuronal excitability.
May modulate cortical excitability in models; leaves open human disease relevance and therapeutic targeting.
The channel pore-forming α subunit Kv4.2 is a major constituent of A-type (I(A)) potassium currents and a key regulator of neuronal membrane excitability. 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 I(A) 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 I(A) channel complexes and a novel regulator of I(A) channel densities and neuronal excitability.
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Marionneau et al. (2012) studied Neuronal excitability. Navβ1 knockdown or knockout vs. Wild-type or non-targeted shRNA was evaluated on IA current densities and action potential repolarization (p=<0.01). Navβ1 interacts with Kv4.2 to increase IA channel densities, and loss of Navβ1 prolongs action potentials and increases repetitive firing in cortical pyramidal neurons.
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