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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30105 - Physiology (including cytology)

Projekt

<a href="/cs/project/GA15-15839S" target="_blank" >GA15-15839S: Regulační mechanizmy nociceptivních ‘transient receptor potential’ iontových kanálů</a><br>

Návaznosti

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

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

Journal of General Physiology

ISSN

0022-1295

e-ISSN

—

Svazek periodika

150

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

20

Strana od-do

1125-1144

Kód UT WoS článku

000440815100009

EID výsledku v databázi Scopus

2-s2.0-85053845013