Electrophysiological and computational analysis of Cav3.2 channel variants associated with familial trigeminal neuralgia

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F22%3A00564838" target="_blank" >RIV/61388963:_____/22:00564838 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11120/22:43924311

Result on the web

<a href="https://doi.org/10.1186/s13041-022-00978-9" target="_blank" >https://doi.org/10.1186/s13041-022-00978-9</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s13041-022-00978-9" target="_blank" >10.1186/s13041-022-00978-9</a>

Result language

angličtina

Original language name

Electrophysiological and computational analysis of Cav3.2 channel variants associated with familial trigeminal neuralgia

Original language description

Trigeminal neuralgia (TN) is a rare form of chronic neuropathic pain characterized by spontaneous or elicited paroxysms of electric shock-like or stabbing pain in a region of the face. While most cases occur in a sporadic manner and are accompanied by intracranial vascular compression of the trigeminal nerve root, alteration of ion channels has emerged as a potential exacerbating factor. Recently, whole exome sequencing analysis of familial TN patients identified 19 rare variants in the gene CACNA1H encoding for Cav3.2T-type calcium channels. An initial analysis of 4 of these variants pointed to a pathogenic role. In this study, we assessed the electrophysiological properties of 13 additional TN-associated Cav3.2 variants expressed in tsA-201 cells. Our data indicate that 6 out of the 13 variants analyzed display alteration of their gating properties as evidenced by a hyperpolarizing shift of their voltage dependence of activation and/or inactivation resulting in an enhanced window current supported by Cav3.2 channels. An additional variant enhanced the recovery from inactivation. Simulation of neuronal electrical membrane potential using a computational model of reticular thalamic neuron suggests that TN-associated Cav3.2 variants could enhance neuronal excitability. Altogether, the present study adds to the notion that ion channel polymorphisms could contribute to the etiology of some cases of TN and further support a role for Cav3.2 channels.

Czech name

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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

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2022

Confidentiality

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

Name of the periodical

Molecular Brain

ISSN

1756-6606

e-ISSN

1756-6606

Volume of the periodical

15

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

14

Pages from-to

91

UT code for WoS article

000885014200002

EID of the result in the Scopus database

2-s2.0-85142124822