Siller, Anita ORCID: 0009-0003-7860-7144, Hofer, Nadja T., Tomagra, Giulia, Burkert, Nicole, Hess, Simon, Benkert, Julia, Gaifullina, Aisylu, Spaich, Desiree, Duda, Johanna, Poetschke, Christina, Vilusic, Kristina, Fritz, Eva Maria ORCID: 0000-0003-2936-2622, Schneider, Toni, Kloppenburg, Peter, Liss, Birgit, Carabelli, Valentina, Carbone, Emilio, Ortner, Nadine Jasmin and Striessnig, Joerg (2022). beta 2-subunit alternative splicing stabilizes Cav2.3 Ca2+ channel activity during continuous midbrain dopamine neuron-like activity. eLife, 11. CAMBRIDGE: eLIFE SCIENCES PUBL LTD. ISSN 2050-084X

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Abstract

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 beta 2-splice variants beta 2a and beta 2e 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 beta 2a- and beta 2e-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 beta 2a- and/or beta 2e-subunits. Thus, beta-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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Siller, AnitaUNSPECIFIEDorcid.org/0009-0003-7860-7144UNSPECIFIED
Hofer, Nadja T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tomagra, GiuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Burkert, NicoleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hess, SimonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Benkert, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gaifullina, AisyluUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spaich, DesireeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Duda, JohannaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Poetschke, ChristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vilusic, KristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fritz, Eva MariaUNSPECIFIEDorcid.org/0000-0003-2936-2622UNSPECIFIED
Schneider, ToniUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kloppenburg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liss, BirgitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carabelli, ValentinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carbone, EmilioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ortner, Nadine JasminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Striessnig, JoergUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-682093
DOI: 10.7554/eLife.67464
Journal or Publication Title: eLife
Volume: 11
Date: 2022
Publisher: eLIFE SCIENCES PUBL LTD
Place of Publication: CAMBRIDGE
ISSN: 2050-084X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GREEN FLUORESCENT PROTEIN; SUBSTANTIA-NIGRA NEURONS; UV-LASER MICRODISSECTION; GATED CALCIUM-CHANNELS; BETA-SUBUNIT; FUNCTIONAL-PROPERTIES; N-TYPE; HIPPOCAMPAL; CURRENTS; EXPRESSIONMultiple languages
BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/68209

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