Referenced in: Kv4.3

Automatically associated channels: Kv1.4 , Kv3.1 , Kv4.2

Title: The kv4.2 potassium channel subunit is required for pain plasticity.

Authors: Hui-Juan Hu, Yarimar Carrasquillo, Farzana Karim, Wonil E Jung, Jeanne M Nerbonne, Thomas L Schwarz, Robert W Gereau

Journal, date & volume: Neuron, 2006 Apr 6 , 50, 89-100

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/16600858

Abstract
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.