Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10956683 | Molecular and Cellular Neuroscience | 2009 | 7 Pages |
Abstract
The voltage-gated sodium channel NaV1.8 is expressed exclusively in nociceptive sensory neurons and plays an important role in pain pathways. NaV1.8 cannot be functionally expressed in non-neuronal cells even in the presence of β-subunits. We have previously identified Pdzd2, a multi PDZ-domain protein, as a potential interactor for NaV1.8. Here we report that Pdzd2 binds directly to the intracellular loops of NaV1.8 and NaV1.7. The endogenous NaV1.8 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 NaV1.8, in dorsal root ganglia of Pdzd2-deficient mice. These findings reveal that Pdzd2 and p11 play collaborative roles in regulation of NaV1.8 expression in sensory neurons.
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Authors
Dongmin Shao, Mark D. Baker, Bjarke Abrahamsen, Francois Rugiero, Misbah Malik-Hall, W.-Y. Louisa Poon, Kathryn S.E. Cheah, Kwok-Ming Yao, John N. Wood, Kenji Okuse,