title: L-type Calcium Channel Cav1.2 Is Required for Maintenance of Auditory Brainstem Nuclei.
abstract: Cav1.2 and Cav1.3 are the major L-type voltage-gated Ca(2+) channels in the CNS. Yet, their individual in vivo functions are largely unknown. Both channel subunits are expressed in the auditory brainstem, where Cav1.3 is essential for proper maturation. Here, we investigated the role of Cav1.2 by targeted deletion in the mouse embryonic auditory brainstem. Similar to Cav1.3, loss of Cav1.2 resulted in a significant decrease in the volume and cell number of auditory nuclei. Contrary to the deletion of Cav1.3, the action potentials of lateral superior olive (LSO) neurons were narrower compared with controls, whereas the firing behavior and neurotransmission appeared unchanged. Furthermore, auditory brainstem responses were nearly normal in mice lacking Cav1.2. Perineuronal nets were also unaffected. The medial nucleus of the trapezoid body underwent a rapid cell loss between postnatal days P0 and P4, shortly after circuit formation. Phosphorylated cAMP response element-binding protein (CREB), nuclear NFATc4, and the expression levels of p75NTR, Fas, and FasL did not correlate with cell death. These data demonstrate for the first time that both Cav1.2 and Cav1.3 are necessary for neuronal survival but are differentially required for the biophysical properties of neurons. Thus, they perform common as well as distinct functions in the same tissue.
authors.affiliation: From the Neurogenetics Group, Center of Excellence Hearing4All, School of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, 26111 Oldenburg, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Ebbers
authors.affiliation: From the Neurogenetics Group, Center of Excellence Hearing4All, School of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, 26111 Oldenburg, Germany.
authors.forename: Somisetty V
authors.initials: SV
authors.lastname: Satheesh
authors.affiliation: the Animal Physiology Group, Department of Biology, University of Kaiserlautern, P. O. Box 3049, 67663 Kaiserslautern, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Janz
authors.affiliation: the Department of Otolaryngology, Hearing Research Centre Tübingen (THRC), Molecular Physiology of Hearing, University of Tübingen, Elfriede Aulhorn Strasse 5, 72076 Tübingen, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Rüttiger
authors.affiliation: the Paul Flechsig Institute of Brain Research, Faculty of Medicine, University Leipzig, Liebigstrasse 19, 04103 Leipzig, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Blosa
authors.affiliation: the Institut für Pharmakologie und Toxikologie, Technische Universität, Biedersteiner Strasse 29, D-80802 München, and.
authors.forename: Franz
authors.initials: F
authors.lastname: Hofmann
authors.affiliation: the Paul Flechsig Institute of Brain Research, Faculty of Medicine, University Leipzig, Liebigstrasse 19, 04103 Leipzig, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Morawski
authors.affiliation: the Animal Physiology Group, Department of Biology, University of Kaiserlautern, P. O. Box 3049, 67663 Kaiserslautern, Germany.
authors.forename: Désirée
authors.initials: D
authors.lastname: Griesemer
authors.affiliation: the Department of Otolaryngology, Hearing Research Centre Tübingen (THRC), Molecular Physiology of Hearing, University of Tübingen, Elfriede Aulhorn Strasse 5, 72076 Tübingen, Germany.
authors.forename: Marlies
authors.initials: M
authors.lastname: Knipper
authors.affiliation: the Animal Physiology Group, Department of Biology, University of Kaiserlautern, P. O. Box 3049, 67663 Kaiserslautern, Germany.
authors.forename: Eckhard
authors.initials: E
authors.lastname: Friauf
authors.affiliation: From the Neurogenetics Group, Center of Excellence Hearing4All, School of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, 26111 Oldenburg, Germany, the Research Center for Neurosensory Science, Carl von Ossietzky University Oldenburg, 26111 Oldenburg, Germany hans.g.nothwang@uni-oldenburg.de.
authors.forename: Hans Gerd
authors.initials: HG
authors.lastname: Nothwang
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001306:Auditory Pathways / Q000166:cytology* / Q000378:metabolism; D001933:Brain Stem / Q000166:cytology* / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000502:physiology*; D016923:Cell Death; D005109:Extracellular Matrix / Q000378:metabolism; D051379:Mice
chemical_list: C514350:CACNA1C protein, mouse; D020746:Calcium Channels, L-Type
keywords: apoptosis; calcium channel; mouse; neuron; signal transduction