PhD Scientific Days 2026

Poster Session 1.A - Molecular Medicine

Molecular Characterization of a TRPM2 Cation Channel Variant Associated with Bipolar Disorder

Előadó neve

Tóth, Ádám

Neptune code

PSKA9S

Előadó munkahelye

Department of Biochemistry, Semmelweis University, Budapest, Hungary

Előadó telefonszáma

06302757507

Előadó e-mail címe

toth.adam@phd.semmelweis.hu

Az előadás címe

Molecular Characterization of a TRPM2 Cation Channel Variant Associated with Bipolar Disorder

Szerző(k) neve és munkahelye

Tóth Ádám¹, Csanády László¹, Bartók Ádám¹

1: Department of Biochemistry, Semmelweis University, Budapest, Hungary

Bemutatás módja

Poszter

Szekció

Poster Session 1.A - Molecular Medicine

Language of the presentation

English

Preferred session

Molecular Medicine

Összefoglaló szövege

TRPM2 is a Ca2+-permeable cation channel that has been recognized as a cellular sensor of oxidative stress. It plays a role in immune cell activation, apoptosis, and oxidative stress response. Recent studies have revealed that TRPM2 also functions as a highly sensitive thermosensor, and thermoregulatory impairments have been observed in gene knockout mice. Moreover, genetic association studies have identified the common TRPM2-D543E variant (MAF = 0.205 globally), which has been linked to bipolar disorder. This variation results in an exchange of an Asp to Glu at position 543.
The aim of this study was to elucidate the functional consequences of D543E substitution in TRPM2 channel activity. To this end, the variant was transiently expressed in HEK cells. Functional characterization was performed in a cell-free system using the inside-out patch-clamp configuration, enabling precise analysis of channel gating properties, ligand sensitivity (Ca²⁺, ADPR), and temperature dependence.
Our results show that the apparent Ca²⁺ affinity of the D543E variant is increased at all tested temperatures (15 °C, 25 °C, and 37 °C), whereas the apparent affinity for ADPR remains largely unchanged. Analysis of channel open probabilities across different temperatures revealed a reduced temperature sensitivity. Due to its increased Ca²⁺ affinity, the variant sustains a higher Ca²⁺ current under physiological conditions (37 °C, 100 nM Ca²⁺, 2 µM ADPR) compared to the wild-type.
In summary, functional analyses revealed differences between the TRPM2-D543E and the wild-type channel. The increased Ca²⁺ sensitivity of the variant leads to enhanced Ca²⁺ influx, which may contribute to elevated neuronal excitability. Furthermore, temperature sensitivity of TRPM2 appears to be finely tuned to the physiological range. As the variant exhibits enhanced activity at the molecular level, this alteration probably shifts thermosensation to non-physiological range, potentially leading to impaired physiological thermoregulation. However, further studies are required to elucidate the role of this variant in the pathogenesis of bipolar disorder.
This work was supported by the Hungarian Centre of Excellence for Molecular Medicine (H-CEMM), National Research, Development and Innovation Office ADVANCED (149640) grant, HUN-REN Office for Supported Research Groups, SE 250+ Excellence PhD Scholarship.

University

Semmelweis University

Supervisor

Bartók Ádám

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

phd.section.field

in doctoral studies after complex exam (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

7434

Start

16:54

End

16:57