Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Neurology. 2006 Nov 14;67(9):1563-7. Epub 2006 Sep 20.

Inherited erythermalgia: limb pain from an S4 charge-neutral Na channelopathy.

Author information

  • 1Department of Neurology, Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, USA.

Abstract

BACKGROUND:

Inherited erythermalgia (also termed "erythromelalgia"), characterized by episodic burning pain in the distal extremities evoked by warmth, has been causally linked with mutations of the Na(v)1.7 sodium channel, which is preferentially expressed in nociceptors. Thus far, Na(v)1.7 mutations within intracellular linker parts of the channel have been physiologically characterized.

OBJECTIVE:

To investigate a Na(v)1.7 erythermalgia mutation that substitutes one uncharged amino acid for another within an S4 segment.

METHODS:

Whole-cell patch-clamp analysis was used to study biophysical properties of wild-type and mutant (F216S) Na(v)1.7 channels in mammalian cells.

RESULTS:

The F216S mutation hyperpolarizes the voltage dependence of activation by 11 mV, accelerates activation, slows deactivation, and enhances the response to slow, small depolarizations.

CONCLUSION:

These results provide a physiologic basis for the linkage to erythermalgia of an Na(v)1.7 mutation that substitutes one uncharged residue for another within an S4 segment of the channel. These changes should increase excitability of nociceptive dorsal root ganglion neurons in which the mutant channel is present, thus contributing to pain.

Comment in

PMID:
16988069
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk