| First Author | Marionneau C | Year | 2012 |
| Journal | J Neurosci | Volume | 32 |
| Issue | 17 | Pages | 5716-27 |
| PubMed ID | 22539834 | Mgi Jnum | J:184603 |
| Mgi Id | MGI:5425165 | Doi | 10.1523/JNEUROSCI.6450-11.2012 |
| Citation | Marionneau C, et al. (2012) The sodium channel accessory subunit Navbeta1 regulates neuronal excitability through modulation of repolarizing voltage-gated K(+) channels. J Neurosci 32(17):5716-27 |
| abstractText | The channel pore-forming alpha 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 Navbeta1. Voltage-clamp and current-clamp recordings revealed that knockdown of Navbeta1 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 Navbeta1. Biochemical and voltage-clamp experiments further demonstrated that Navbeta1 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 Navbeta1 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. |
