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This activity may contribute to the selective degeneration of these neurons in Parkinson\u2019s disease (PD) since Cav2.3-knockout is neuroprotective in a PD mouse model. Here, we show that in tsA-201-cells the membrane-anchored \u03b22-splice variants \u03b22a and \u03b22e are required to stabilize Cav2.3 gating properties allowing sustained Cav2.3 availability during simulated pacemaking and enhanced Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -currents during bursts. We confirmed the expression of \u03b22a- and \u03b22e-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 Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -currents with voltage-dependent gating properties that suggest modulation by \u03b22a- and\/or \u03b22e-subunits. Thus, \u03b2-subunit alternative splicing may prevent a fraction of Cav2.3 channels from inactivation in continuously active, highly vulnerable SN DA neurons, thereby also supporting Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signals contributing to the (patho)physiological role of Cav2.3 channels in PD.\n                  <\/jats:p>","DOI":"10.7554\/elife.67464","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T06:00:48Z","timestamp":1657087248000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.67464","source":"Crossref","is-referenced-by-count":24,"title":["\u03b22-subunit alternative splicing stabilizes Cav2.3 Ca2+ channel activity during continuous midbrain dopamine neuron-like activity"],"prefix":"10.7554","volume":"11","author":[{"given":"Anita","family":"Siller","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/054pv6659","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of 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