title: UCP3 Regulates Single-Channel Activity of the Cardiac mCa1.
abstract: Mitochondrial Ca(2+) uptake (mCa(2+) uptake) is thought to be mediated by the mitochondrial Ca(2+) uniporter (MCU). UCP2 and UCP3 belong to a superfamily of mitochondrial ion transporters. Both proteins are expressed in the inner mitochondrial membrane of the heart. Recently, UCP2 was reported to modulate the function of the cardiac MCU related channel mCa1. However, the possible role of UCP3 in modulating cardiac mCa(2+) uptake via the MCU remains inconclusive. To understand the role of UCP3, we analyzed cardiac mCa1 single-channel activity in mitoplast-attached single-channel recordings from isolated murine cardiac mitoplasts, from adult wild-type controls (WT), and from UCP3 knockout mice (UCP3(-/-)). Single-channel registrations in UCP3(-/-) confirmed a murine voltage-gated Ca(2+) channel, i.e., mCa1, which was inhibited by Ru360. Compared to WT, mCa1 in UCP3(-/-) revealed similar single-channel characteristics. However, in UCP3(-/-) the channel exhibited decreased single-channel activity, which was insensitive to adenosine triphosphate (ATP) inhibition. Our results suggest that beyond UCP2, UCP3 also exhibits regulatory effects on cardiac mCa1/MCU function. Furthermore, we speculate that UCP3 might modulate previously described inhibitory effects of ATP on mCa1/MCU activity as well.
authors.affiliation: Department of Internal Medicine II, Paracelsus Medical University, Muellner Hauptstr. 48, A-5020, Salzburg, Austria. lukas.motloch@pmu.ac.at.
authors.forename: Lukas J
authors.initials: LJ
authors.lastname: Motloch
authors.affiliation: Department of Internal Medicine II, Paracelsus Medical University, Muellner Hauptstr. 48, A-5020, Salzburg, Austria.
authors.forename: Tina
authors.initials: T
authors.lastname: Gebing
authors.affiliation: Department of Internal Medicine II, Paracelsus Medical University, Muellner Hauptstr. 48, A-5020, Salzburg, Austria.
authors.forename: Sara
authors.initials: S
authors.lastname: Reda
authors.affiliation: Department of Internal Medicine II, Paracelsus Medical University, Muellner Hauptstr. 48, A-5020, Salzburg, Austria.
authors.forename: Astrid
authors.initials: A
authors.lastname: Schwaiger
authors.affiliation: Department of Internal Medicine II, Paracelsus Medical University, Muellner Hauptstr. 48, A-5020, Salzburg, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Wolny
authors.affiliation: Department of Internal Medicine II, Paracelsus Medical University, Muellner Hauptstr. 48, A-5020, Salzburg, Austria.
authors.forename: Uta C
authors.initials: UC
authors.lastname: Hoppe
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D005260:Female; D008297:Male; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D018345:Mice, Knockout; D008929:Mitochondria, Heart / Q000378:metabolism*; D012508:Sarcolemma / Q000378:metabolism; D000071247:Uncoupling Protein 3 / Q000235:genetics / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D000071247:Uncoupling Protein 3; C034703:mitochondrial calcium uniporter; D000255:Adenosine Triphosphate; D002118:Calcium
keywords: ATP; Calcium; Mitochondria; Mitochondrial calcium uniporter; UCP3; mCa1