| First Author | Hu HJ | Year | 2006 |
| Journal | Neuron | Volume | 50 |
| Issue | 1 | Pages | 89-100 |
| PubMed ID | 16600858 | Mgi Jnum | J:110968 |
| Mgi Id | MGI:3652461 | Doi | 10.1016/j.neuron.2006.03.010 |
| Citation | Hu HJ, et al. (2006) The kv4.2 potassium channel subunit is required for pain plasticity. Neuron 50(1):89-100 |
| abstractText | A-type potassium currents are important determinants of neuronal excitability. In spinal cord dorsal horn neurons, A-type currents are modulated by extracellular signal-regulated kinases (ERKs), which mediate central sensitization during inflammatory pain. Here, we report that Kv4.2 mediates the majority of A-type current in dorsal horn neurons and is a critical site for modulation of neuronal excitability and nociceptive behaviors. Genetic elimination of Kv4.2 reduces A-type currents and increases excitability of dorsal horn neurons, resulting in enhanced sensitivity to tactile and thermal stimuli. Furthermore, ERK-mediated modulation of excitability in dorsal horn neurons and ERK-dependent forms of pain hypersensitivity are absent in Kv4.2(-/-) mice compared to wild-type littermates. Finally, mutational analysis of Kv4.2 indicates that S616 is the functionally relevant ERK phosphorylation site for modulation of Kv4.2-mediated currents in neurons. These results show that Kv4.2 is a downstream target of ERK in spinal cord and plays a crucial role in pain plasticity. |
