A multi PDZ-domain protein Pdzd2 contributes to functional expression of sensory neuron-specific sodium channel Na sub(V)1.8

• Published in: Molecular and cellular neuroscience Vol. 42; no. 3; pp. 219 - 225
• Main Authors: Shao, D, Baker, MD, Abrahamsen, B, Rugiero, F, Malik-Hall, M, Poon, WYL, Cheah, KSE, Yao, K M, Wood, J N, Okuse, K
• Format: Journal Article
• Language: English
• Published: 01.10.2009
• ISSN: 1044-7431
• DOI: 10.1016/j.mcn.2009.07.003

The voltage-gated sodium channel Na sub(V)1.8 is expressed exclusively in nociceptive sensory neurons and plays an important role in pain pathways. Na sub(V)1.8 cannot be functionally expressed in non-neuronal cells even in the presence of beta -subunits. We have previously identified Pdzd2, a multi PDZ-domain protein, as a potential interactor for Na sub(V)1.8. Here we report that Pdzd2 binds directly to the intracellular loops of Na sub(V)1.8 and Na sub(V)1.7. The endogenous Na sub(V)1.8 current in sensory neurons is inhibited by antisense- and siRNA-mediated downregulation of Pdzd2. However, no marked change in pain behaviours is observed in Pdzd2-decificent mice. This may be due to compensatory upregulation of p11, another regulatory factor for Na sub(V)1.8, in dorsal root ganglia of Pdzd2-deficient mice. These findings reveal that Pdzd2 and p11 play collaborative roles in regulation of Na sub(V)1.8 expression in sensory neurons.