PhD Scientific Days 2024

Poster Session E - Molecular Medicine 2.

Molecular Characterization of Pathological TRPM2 Cation Channel Variants

Előadó neve

Mr. Tóth, Ádám

Neptun code

PSKA9S

Előadó munkahelye

Semmelweis University, Department of Biochemistry

Előadó telefonszáma

+36302757507

Előadó e-mail címe

toth.adam@phd.semmelweis.hu

Az előadás címe

Molecular Characterization of Pathological TRPM2 Cation Channel Variants

Szerző(k) neve és munkahelye

Ádám Tóth¹, Bartók Ádám¹, Csanády László¹

1: Semmelweis University, Department of Biochemistry

Bemutatás módja

Poszter

Szekció

Poster Session E - Molecular Medicine 2.

Language of the presentation

English

Preferred session

Molecular Medicine

Összefoglaló szövege

The Ca2+-permeable cation channel TRPM2 gained traction due to its exceedingly high temperature sensitivity. Accordingly, physiological studies have found that KO mice possess impaired temperature homeostasis. The central heat adjustment is restricted to the hypothalamic preoptic area, where TRPM2-expressing neurons were identified. Besides the heat sensitivity, this ion channel has widespread physiological roles, such as cytokine production, apoptosis or oxidative stress response.. Moreover, genetic association studies have found linkage between point mutations in TRPM2 and bipolar disorder (D543E, R755C) or amyotrophic lateral sclerosis and Parkinson's dementia (P1018L).
Investigation of these channel variants lags behind. Thus we aim to examine them in an experimental arrangement where the essential intracellular agents (adenosine diphosphate ribose (ADPR), Ca2+ and phosphatidylinositol 4,5-bisphosphate (PIP2)) can be monitored in order to better understand their role in pathophysiology.
The TRPM2 variants are transiently expressed in HEK-293 cells. Functional measurements are performed in a cell-free environment, using inside-out patch clamp configuration. This method enables the recording of micro- and macroscopic currents, as well as the efficient exchange of intracellular ligands. With this method, the ligand sensitivity, gating parameters, inactivation kinetics, and temperature dependence of individual channel variants can be accurately defined.
Functional studies showed no difference neither in inactivation, nor in ligand senstivity in R755C and P1018L compared to wild-type channels. Interestingly, D543E mutation resulted in increased Ca2+-sensitivity at room temperature and this difference is even higher at elevated temperature (37°C) while leaving the ADPR-sensitivity intact.
Single channel analysis (unitary conductance, open probability, permeability) at different temperatures might reveal the phenomenon behind the increased Ca2+-sensitivity of D543E. Further examination in vivo is required to understand how this altered functionality contributes to the complex etiology of bipolar disorder.
This work is funded by Hungarian Centre of Excellence for Molecular Medicine (H-CEMM), János Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00103/20), HUN-REN Office for Supported Research Groups and 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.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

7434

Start

15:15

End

15:18