PhD Scientific Days 2024

Poster Session M - Cardiovascular Medicine and Research 1.

Investigation of Kv1.5 Ion Channel Mutants in Pulmonary Arterial Hypertension

Előadó neve

Ms. Csáki, Réka, MSc

Neptun code

KA84WY

Előadó munkahelye

Semmelweis University, Department of Physiology

Előadó telefonszáma

+36304100841

Előadó e-mail címe

csaki.reka@phd.semmelweis.hu

Az előadás címe

Investigation of Kv1.5 Ion Channel Mutants in Pulmonary Arterial Hypertension

Szerző(k) neve és munkahelye

Réka Csáki¹, Vasile Foris², Christina Eichstaedt^3,4,5, Alice Dobolyi⁶, Ekkehard Gruening^3,4,5, Frigyes Mészáros⁶, Chandran Nagaraj², János Almássy⁶, Andrea Olschewski², Horst Olschewski^2,7, Péter Enyedi⁶

1: Semmelweis University
2: Ludwig Boltzmann Institute for Lung Vascular Research
3: Center for Pulmonary Hypertension, Thoraxklinik Heidelberg gGmbH. Heidelberg University Hospital
4: Translational Lung Research Center Heidelberg, German Center for Lung Research
5: Laboratory for Molecular Diagnostics, Institute of Human Genetics, Heidelberg University
6: Semmelweis University, Department of Physiology
7: Medical University of Graz, Internal Medicine

Bemutatás módja

Poszter

Szekció

Poster Session M - Cardiovascular Medicine and Research 1.

Language of the presentation

English

Preferred session

Cardiovascular Medicine and Research

Összefoglaló szövege

Pulmonary arterial hypertension (PAH) is a serious disease characterized by increased pulmonary small arterial resistance as a result vasocontriction and vascular remodelling, terminally leading to right heart failure. It can develop on the basis of pathological ion channel activities of the smooth muscle cells in the small pulmonary arteries (PASMC) leading to depolarisation and elevation of cytoplasmic [Ca2+]. In these cells a set of different K+ channels are essential in the maintenance of the physiological "hyperpolarized" membrane potential. Our previous studies, showed that TREK-1 (K2P) channel in PASMCs of healthy donors and idiopathic PAH patients. Our results suggested that pharmacological activation of TREK-1 may even be considered as a therapeutic option in PAH. The voltage dependent K+ channel; Kv1.5 is also expressed in PASMCs and its loss of function mutations have been associated with PAH. A targeted screening (performed by our Heidelberg collaborators) in a database of PAH patients identified several -until now uncharacterized- Kv1.5 mutations.
Aims
Our experiments aim to better understand the relationship between the altered function of various K+ channels and the development of PAH. In the present studies we investigated the consequence of the identified mutations on Kv1.5 channel function.
Methods
Seven of the identified Kv1.5 channel mutants were created and cloned into different expression vectors. Their electrophysiological properties were analysed in heterologous expression experiments first in Xenopus laevis oocytes then in HEK cells. In addition, we aim to infect healthy PASMCs with the functionally impaired mutant Kv1.5 construct to investigate whether a negative dominant effect becomes apparent in such heterozygous conditions.
Results
In the Xenopus oocyte system, the current of the G435R mutant was 87 +/- 1.3 % lower than that of the wild type (WT), with slower activation and minimal inactivation of the mutant. In coexpression experiments (WT:G435R), we observed reduced inactivation compared to the WT channel at maintained depolarising voltage.
Conclusion
The G435R Kv1.5 mutant may a play role in IPAH disease, but further experiments are needed to answer this question.
Funding
Supported by SE250+ excellence PhD scholarship and by the NKFIH TKP2021-EGA-24 provided by the Ministry of Innovation and Technology of Hungary.

University

Semmelweis University

Supervisor

Péter Enyedi M.D., D.Sc.

Publication of my abstract

I do not 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

7416

Start

16:15

End

16:18