Heat-resistant action potentials require TTX-resistant sodium channels Na(V)1.8 and Na(V)1.9

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F18%3A00492835" target="_blank" >RIV/67985823:_____/18:00492835 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1085/jgp.201711786" target="_blank" >http://dx.doi.org/10.1085/jgp.201711786</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1085/jgp.201711786" target="_blank" >10.1085/jgp.201711786</a>

Result language

angličtina

Original language name

Heat-resistant action potentials require TTX-resistant sodium channels Na(V)1.8 and Na(V)1.9

Original language description

Damage-sensing nociceptors in the skin provide an indispensable protective function thanks to their specialized ability to detect and transmit hot temperatures that would block or inflict irreversible damage in other mammalian neurons. Here we show that the exceptional capacity of skin C-fiber nociceptors to encode noxiously hot temperatures depends on two tetrodotoxin (TTX)-resistant sodium channel a-subunits: Na(V)1.8 and Na(V)1.9. We demonstrate that Na(V)1.9, which is commonly considered an amplifier of subthreshold depolarizations at 20 degrees C, undergoes a large gain of function when temperatures rise to the pain threshold. We also show that this gain of function renders Na(V)1.9 capable of generating action potentials with a clear inflection point and positive overshoot. In the skin, heat-resistant nociceptors appear as two distinct types with unique and possibly specialized features: one is blocked by TTX and relies on Na(v)1.9, and the second type is insensitive to TTX and composed of both Na(V)1.8 and Na(V)1.9. Independent of rapidly gated TTX-sensitive Na-V channels that form the action potential at pain threshold, Na(V)1.8 is required in all heat-resistant nociceptors to encode temperatures higher than similar to 46 degrees C, whereas Na(V)1.9 is crucial for shaping the action potential upstroke and keeping the Na(V)1.8 voltage threshold within reach.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30105 - Physiology (including cytology)

Project

<a href="/en/project/GA15-15839S" target="_blank" >GA15-15839S: Regulatory mechanisms of nociceptive transient receptor potential ion channels</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of General Physiology

ISSN

0022-1295

e-ISSN

—

Volume of the periodical

150

Issue of the periodical within the volume

8

Country of publishing house

US - UNITED STATES

Number of pages

20

Pages from-to

1125-1144

UT code for WoS article

000440815100009

EID of the result in the Scopus database

2-s2.0-85053845013