PhD Scientific Days 2026

Poster Session 3.U - Molecular Medicine

Investigation of the calcium-dependent regulation of the human TREK-1 background potassium channel

Name of the presenter

Debreczeni, Dorina

Institute/workplace of the presenter

Department of Physiology, Semmelweis University

Authors

Dorina Debreczeni¹, Réka Csáki¹
1: Department of Physiology, Semmelweis University

Text of the abstract

TREK-1 as a member of the two-pore-domain (K2P) potassium channel family, plays an important role in regulation of neuronal excitability and mechanosensitivity. Our research group previously demonstrated that another member of the K2P channel family, the TRESK channel, is activated by the direct binding of calcineurin phosphatase. The role of G-protein-coupled receptor-linked calcium-dependent signaling pathways has already been demonstrated for numerous K2P channels, but less information is available in the literature regarding the regulation of the TREK-1 channel by calcium.
Our research group has previously studied TREK-1/TRESK heterodimeric channels. We observed that the calcium ionophore ionomycin also affects TREK-1 control channels. The aim of the present study is to elucidate the processes underlying the calcium-dependent regulation of the TREK-1 channel.
The cRNA for human TREK-1 and M1 Gq-coupled receptor was synthesized in vitro and microinjected into Xenopus laevis oocytes. The effect of M1 receptor stimulation on the TREK-1 channel was examined in a heterologous expression system using the two-electrode voltage-clamp technique. During our experiments, the M1 receptor was stimulated with carbachol (1 μM). For certain measurements, we injected EGTA (2.5 nmol) into the cells 1–2 hours prior to the measurement.
The co-expression of the M1 receptor followed by stimulation with carbachol leads to activation of the TREK-1 channel. We were also able to prove the calcium dependence of the ’run-down’ phenomenon, as we observed a slowing of the run-down process in the presence of intracellular EGTA (n = 4-6, p < 0.02), which we were able to slow down even further (n = 4-6, p < 0.005) using a sustained hyperpolarization measurement protocol (-100 mV holding potential).
We were able to demonstrate that the activation of the TREK-1 channel is calcium-dependent by stimulating the M1 receptor. Cytoplasmic Ca2+ levels may also be a key factor underlying the ’run-down’ phenomenon observed during TREK-1 channel measurements. Our studies may contribute to a better understanding of the function of this channel which also plays a role in pain perception.
Supported by the 2025-2.1.1-EKÖP-2025-00014 University Research Scholarship Programme of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund.