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We investigate molecular mechanisms of nociception and thermosensation by focusing on thermosensitive transient receptor potential (TRP) ion channels. These channels are specifically expressed in primary nociceptive neurons and work in concert to detect potentially damaging stimuli and transduce them into pain signalling.
The goal of our research is to understand the physiological or pathophysiological significance of specific subclasses of TRP ion channels involved in the detection of noxious thermal, mechanical and chemical stimuli, through deciphering molecular and biophysical principles of their operational features.
We use electrophysiological and microfluorometric techniques, mainly patch-clamp recording at whole-cell and single-channel levels. For a more detailed understanding of TRP ion channel activation mechanisms we also use biochemistry and molecular biology combined with molecular modelling.
Temperature thresholds for activation range of thermosensitive TRP ion channels in mammals (TRPM8, TRPC5, TRPA1, TRPM2-5, TRPV1-4), from lower to higher: TRPA1 (PDB: 6PQQ), TRPM8 (6O77), TRPC5 (7D4P), TRPV4 (7AA5), TRPM2-3 (TRPM2 shown, 6PUO), TRPA1 (6PQQ), TRPV1-3 (TRPV3 shown, 6MHV). Temperatures below 15° and over 43°C cause pain sensation in mammals; therefore, several of the thermosensitive TRP ion channels can be viewed as nociceptive detectors. TRP receptors ordered by increasing temperature of their activation threshold.
Recent review papers:
[1] Vlachova, V., Barvik, I., & Zimova, L. (2024). Human Transient Receptor Potential Ankyrin 1 Channel: Structure, Function, and Physiology. Macromolecular Protein Complexes V: Structure and Function, 207-244. https://doi.org/10.1007/978-3-031-58843-3_10
[2] Ptakova, A., & Vlachova, V. (2024). Thermosensing ability of TRPC5: current knowledge and unsettled questions. The Journal of Physiological Sciences, 74(1), 50. https://doi.org/10.1186/s12576-024-00942-3
[3] Khare, P., Chand, J., Ptakova, A., Liguori, R., Ferrazzi, F., Bishnoi, M., Vlachova, V. and Zimmermann, K. (2024). The TRPC5 receptor as pharmacological target for pain and metabolic disease. Pharmacology & Therapeutics, 108727. https://doi.org/10.1016/j.pharmthera.2024.108727
Ongoing Studies:
