Detail

Keywords

Effects of drugs on ion channels; Neuropharmacology; Neurophysiology; Patch-Clamp Techniques; Potassium Channels, Voltage-Gated

Research interests

I am interested to understand the modulation of ion channels involved in controlling the excitability of peripheral neurons. Two ion channel families that control excitability are the voltage-gated potassium channel family Kv7 and calcium-activated chloride channels. The activity of both ion channel families is controlled by Gq-coupled receptors via depletion of PIP2 and/ or increase in intracellular calcium. One one hand I want to investigate the endogenous modulation of these channels via G-protein coupled receptors for example in sensory neurons which helps us understand how inflammatory mediators affect nociception. On the other hand I investigate small molecule modulators of these ion channels which might prove useful as analgesics. Recently, I could show that the paracetamol metabolite NAPQI reduces neuronal excitability via Kv7 channels, which contributes to the therapeutic action of paracetamol.

Techniques, methods & infrastructure

Primary neuronal cultures: of superior cervical ganglion (SCG) neurons, dorsal root ganglia (DRG) neurons, and dorsal horn cultures; Voltage- and current-clamp recordings; Imaging techniques; Combined fluorescence imaging and patch-clamp recordings

Grants

• Kv7 channels as targets for paracetamol (2019)
  Source of Funding: FWF (Austrian Science Fund), Principal Investigator Project
  Principal Investigator

Selected publications

1. Ray, S. et al. (2024) ‘A triple cysteine motif as major determinant of the modulation of neuronal KV7 channels by the paracetamol metabolite N‐acetyl‐p‐benzo quinone imine’, British Journal of Pharmacology, 181(16), pp. 2851–2868. Available at: https://doi.org/10.1111/bph.16380.
2. Losgott, T. et al. (2024) ‘The paracetamol metabolite N‐acetyl‐4‐benzoquinoneimine (NAPQI) prevents modulation of KV7 channels via G‐protein coupled receptors by interference with PIP2 and Ca2+ sensitivity’, British Journal of Pharmacology, 182(6), pp. 1341–1357. Available at: https://doi.org/10.1111/bph.17419.
3. Stampf, J.-L. et al. (2022) ‘Analgesic Action of Acetaminophen via Kv7 Channels’, International Journal of Molecular Sciences, 24(1), p. 650. Available at: https://doi.org/10.3390/ijms24010650.
4. Ray, S. et al. (2018) ‘The paracetamol metabolite N-acetylp-benzoquinone imine reduces excitability in first- and second-order neurons of the pain pathway through actions on KV7 channels’, Pain, 160(4), pp. 954–964. Available at: https://doi.org/10.1097/j.pain.0000000000001474.
5. Losgott, T. et al. (2025) ‘Gaussian white noise stimulation as an alternative method to excite sensory neurons’, Frontiers in Pharmacology, 16. Available at: https://doi.org/10.3389/fphar.2025.1561905.