Calcium Channels, L-Type; Calcium Signaling; Epilepsy; Hippocampus; Mitochondria; Patch-Clamp Techniques
Research in the group focuses on the role of various ion channels in the electrical activities of nerve cells. The aim of our work is to understand their implication in normal and abnormal discharge patterns. Our ultimate goal is to assess the potential targetability of these channels in neurological diseases. Currently we are investigating these questions with respect to L-type voltage-gated calcium channels (LTCCs). We identified a precipitating role of enhanced levels of LTCC activity in interictal discharge patterns, so called paroxysmal depolarization shifts (PDS), which are now increasingly understood as neuropathologic events, most probably exceeding epileptogenic mechanisms.
Techniques, methods & infrastructure
We primarily perform current-clamp experiments to record membrane voltage using the minimally invasive perforated-patch mode. Voltage clamp experiments are employed for further analysis. In addition, we use fluorescence-based indicators and confocal microscopy to study calcium signaling and cellular metabolism. The investigations are performed on primary cultures of hippocampal neurons derived from rats and genetically modified mice strains.
- Hotka, M. et al., 2020. L-type Ca2+ channel–mediated Ca2+ influx adjusts neuronal mitochondrial function to physiological and pathophysiological conditions. Science Signaling, 13(618), p.eaaw6923. Available at: http://dx.doi.org/10.1126/scisignal.aaw6923.
- Kubista, H., Boehm, S. & Hotka, M., 2019. The Paroxysmal Depolarization Shift: Reconsidering Its Role in Epilepsy, Epileptogenesis and Beyond. International Journal of Molecular Sciences, 20(3), p.577. Available at: http://dx.doi.org/10.3390/ijms20030577.
- Stiglbauer, V. et al., 2017. Cav1.3 channels play a crucial role in the formation of paroxysmal depolarization shifts in cultured hippocampal neurons. Epilepsia, 58(5), pp.858–871. Available at: http://dx.doi.org/10.1111/epi.13719.
- Treven, M. et al., 2015. The anticonvulsant retigabine is a subtype selective modulator of GABAAreceptors. Epilepsia, 56(4), pp.647–657. Available at: http://dx.doi.org/10.1111/epi.12950.
- Hasreiter, J. et al., 2014. Cav1.2 and Cav1.3 L-type calcium channels operate in a similar voltage range but show different coupling to Ca2+-dependent conductances in hippocampal neurons. American Journal of Physiology-Cell Physiology, 306(12), pp.C1200–C1213. Available at: http://dx.doi.org/10.1152/ajpcell.00329.2013.