| Autor: |
Anita Siller, Nadja T Hofer, Giulia Tomagra, Nicole Burkert, Simon Hess, Julia Benkert, Aisylu Gaifullina, Desiree Spaich, Johanna Duda, Christina Poetschke, Kristina Vilusic, Eva Maria Fritz, Toni Schneider, Peter Kloppenburg, Birgit Liss, Valentina Carabelli, Emilio Carbone, Nadine Jasmin Ortner, Jörg Striessnig |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
eLife, Vol 11 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2050-084X |
| DOI: |
10.7554/eLife.67464 |
| Popis: |
In dopaminergic (DA) Substantia nigra (SN) neurons Cav2.3 R-type Ca2+-currents contribute to somatodendritic Ca2+-oscillations. This activity may contribute to the selective degeneration of these neurons in Parkinson’s disease (PD) since Cav2.3-knockout is neuroprotective in a PD mouse model. Here, we show that in tsA-201-cells the membrane-anchored β2-splice variants β2a and β2e are required to stabilize Cav2.3 gating properties allowing sustained Cav2.3 availability during simulated pacemaking and enhanced Ca2+-currents during bursts. We confirmed the expression of β2a- and β2e-subunit transcripts in the mouse SN and in identified SN DA neurons. Patch-clamp recordings of mouse DA midbrain neurons in culture and SN DA neurons in brain slices revealed SNX-482-sensitive R-type Ca2+-currents with voltage-dependent gating properties that suggest modulation by β2a- and/or β2e-subunits. Thus, β-subunit alternative splicing may prevent a fraction of Cav2.3 channels from inactivation in continuously active, highly vulnerable SN DA neurons, thereby also supporting Ca2+ signals contributing to the (patho)physiological role of Cav2.3 channels in PD. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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