NaV1.7 is a voltage-gated sodium channel. This
means that it’s a group of transmembrane proteins that together form a tunnel
through which sodium ions can pass. The passage isn’t open all the time though.
Only a localized difference in electrical potential (voltage) will open the
gate, allowing sodium ions to enter the cell from the outside. This, in turn,
alters the microenvironment of the next stretch of membrane. In this way, a
signal is rapidly propagated along the length of the cell. Each type of ion can
only enter a cell through a matching ion channel (sodium ions through sodium
channels, potassium ions through potassium channels, etc). What makes NaV1.7
special is that it’s associated with the sensation of pain.
Diagram of ion channel.
Credit Sandwalk.
If
your NaV1.7 channels are inactive (permanently closed) you might not
feel any pain at all (which is a lot worse than it seems). If the channels are
overactive (unable to close) you’ll have chronic pain. This is the case for the
unfortunate sufferers of a condition called inherited erythromelalgia, a.k.a.
‘Man on Fire Syndrome’. You can guess how that feels. To make things worse, some varieties of NaV1.7
channels do not respond well to medicines designed to stabilize ion channels.
Yang Yang and her colleagues from
Yale University School of Medicine were able to study the effects of specific
mutations within the NaV1.7 channels
that render them more or less sensitive to pain medicines. Apparently, genotype does make a significant difference in how well people will respond to treatment. The scientists
suggest that chronic pain patients routinely have their ion channels screened
for subtype as a part of their treatment regimens. This may lead to the illusive
cure for at least some types of chronic pain.
Yang, Y., Dib-Hajj, S., Zhang, J., Zhang, Y., Tyrrell, L., Estacion, M., & Waxman, S. (2012). Structural modelling and mutant cycle analysis predict pharmacoresponsiveness of a Nav1.7 mutant channel Nature Communications, 3 DOI: 10.1038/ncomms2184
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