| Autor: |
Spaich D, Giulia Tomagra, Eva Maria Fritz, Nicole Wiederspohn, Nadine J. Ortner, Anita Siller, Simon Hess, Emilio Carbone, Peter Kloppenburg, Aisylu S. Gaifullina, Toni Schneider, Jörg Striessnig, Nadja T. Hofer, Carabelli, Johanna Duda, Julia Benkert, Birgit Liss, Vilusic K, Christina Poetschke |
| Rok vydání: |
2021 |
| Předmět: |
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| Popis: |
In dopaminergic (DA) substantia nigra (SN) neurons Cav2.3 R-type Ca2+-currents contribute to somatodendritic Ca2+-oscillations. These 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. However, the typical Cav2.3 gating would predict complete channel inactivation during SN DA neuronal firing. Here we show that in tsA-201-cells the membrane-anchored β2-splice variants β2a and β2e 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-subunits in the SN and identified SN DA neurons. Patch-clamp recordings of SN DA neurons in mouse brain slices revealed R-type Ca2+-currents similar to β2a- or β2e-stabilized Cav2.3-currents and recordings in cultured murine DA neurons confirmed their activity during pacemaking. Taken together, our data support an important (patho)physiological role of β-subunit alternative splicing for Cav2.3 Ca2+-signaling in highly vulnerable SN DA neurons. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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