A concerted action of L- and T-type Ca(2+) channels regulates locus coeruleus pacemaking.
Identifieur interne : 000846 ( Main/Exploration ); précédent : 000845; suivant : 000847A concerted action of L- and T-type Ca(2+) channels regulates locus coeruleus pacemaking.
Auteurs : Lina A. Matschke [Allemagne] ; Mirjam Bertoune [Allemagne] ; Jochen Roeper [Allemagne] ; Terrance P. Snutch [Canada] ; Wolfgang H. Oertel [Allemagne] ; Susanne Rinné [Allemagne] ; Niels Decher [Allemagne]Source :
- Molecular and cellular neurosciences [ 1095-9327 ] ; 2015.
English descriptors
- KwdEn :
- Action Potentials (drug effects), Action Potentials (physiology), Animals, Biophysics, Calcium Channel Agonists (pharmacology), Calcium Channel Blockers (pharmacology), Calcium Channels, L-Type (genetics), Calcium Channels, L-Type (metabolism), Calcium Channels, T-Type (genetics), Calcium Channels, T-Type (metabolism), Electric Stimulation, Green Fluorescent Proteins (genetics), Green Fluorescent Proteins (metabolism), In Vitro Techniques, Locus Coeruleus (cytology), Male, Mice, Mice, Inbred C57BL, Neurons (drug effects), Neurons (physiology), Patch-Clamp Techniques, Sodium Channel Blockers (pharmacology), Statistics, Nonparametric, Tetrodotoxin (pharmacology).
- MESH :
- chemical , genetics : Calcium Channels, L-Type, Calcium Channels, T-Type, Green Fluorescent Proteins.
- chemical , metabolism : Calcium Channels, L-Type, Calcium Channels, T-Type, Green Fluorescent Proteins.
- chemical , pharmacology : Calcium Channel Agonists, Calcium Channel Blockers, Sodium Channel Blockers, Tetrodotoxin.
- cytology : Locus Coeruleus.
- drug effects : Action Potentials, Neurons.
- physiology : Action Potentials, Neurons.
- Animals, Biophysics, Electric Stimulation, In Vitro Techniques, Male, Mice, Mice, Inbred C57BL, Patch-Clamp Techniques, Statistics, Nonparametric.
Abstract
Dysfunction of noradrenergic locus coeruleus (LC) neurons is involved in psychiatric and neurodegenerative diseases and is an early hallmark of Parkinson's disease (PD). The analysis of ion channels underlying the autonomous electrical activity of LC neurons, which is ultimately coupled to cell survival signaling pathways, can lead to a better understanding of the vulnerability of these neurons. In LC neurons somatodendritic Ca(2+) oscillations, mediated by L-type Ca(2+) channels, accompany spontaneous spiking and are linked to mitochondrial oxidant stress. However, the expression and functional implication of low-threshold activated T-type Ca(2+) channels in LC neurons were not yet studied. To this end we performed RT-PCR expression analysis in LC neurons. In addition, we utilized slice patch clamp recordings of in vitro brainstem slices in combination with L-type and T-type Ca(2+) channel blockers. We found the expression of a distinct set of L-type and T-type Ca(2+) channel subtypes mediating a pronounced low-threshold activated Ca(2+) current component. Analyzing spike trains, we revealed that neither L-type Ca(2+) channel nor T-type Ca(2+) channel blockade alone leads to a change in firing properties. In contrast, a combined application of antagonists significantly decreased the afterhyperpolarization amplitude, resulting in an increased firing frequency. Hence, we report the functional expression of T-type Ca(2+) channels in LC neurons and demonstrate their role in increasing the robustness of LC pacemaking by working in concert with Cav1 channels.
DOI: 10.1016/j.mcn.2015.08.012
PubMed: 26319746
Affiliations:
- Allemagne, Canada
- District de Darmstadt, District de Giessen, Hesse (Land)
- Francfort-sur-le-Main, Marbourg
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Le document en format XML
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Matschke</name><affiliation wicri:level="3"><nlm:affiliation>Institut für Physiologie und Pathophysiologie, Abteilung Vegetative Physiologie, Universität Marburg, 35037 Marburg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institut für Physiologie und Pathophysiologie, Abteilung Vegetative Physiologie, Universität Marburg, 35037 Marburg</wicri:regionArea><placeName><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Giessen</region><settlement type="city">Marbourg</settlement></placeName></affiliation></author><author><name sortKey="Bertoune, Mirjam" sort="Bertoune, Mirjam" uniqKey="Bertoune M" first="Mirjam" last="Bertoune">Mirjam Bertoune</name><affiliation wicri:level="3"><nlm:affiliation>Institut für Anatomie und Zellbiologie, Medizinische Zellbiologie, Universität Marburg, 35037 Marburg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institut für Anatomie und Zellbiologie, Medizinische Zellbiologie, Universität Marburg, 35037 Marburg</wicri:regionArea><placeName><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Giessen</region><settlement type="city">Marbourg</settlement></placeName></affiliation></author><author><name sortKey="Roeper, Jochen" sort="Roeper, Jochen" uniqKey="Roeper J" first="Jochen" last="Roeper">Jochen Roeper</name><affiliation wicri:level="3"><nlm:affiliation>Institut für Neurophysiologie, Neuroscience Center, 60590 Frankfurt, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institut für Neurophysiologie, Neuroscience Center, 60590 Frankfurt</wicri:regionArea><placeName><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Darmstadt</region><settlement type="city">Francfort-sur-le-Main</settlement></placeName></affiliation></author><author><name sortKey="Snutch, Terrance P" sort="Snutch, Terrance P" uniqKey="Snutch T" first="Terrance P" last="Snutch">Terrance P. 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Oertel</name><affiliation wicri:level="3"><nlm:affiliation>Klinik für Neurologie, Philipps Universität Marburg, 35037 Marburg, Germany; Charitable Hertie Foundation, Frankfurt/Main, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Klinik für Neurologie, Philipps Universität Marburg, 35037 Marburg, Germany; Charitable Hertie Foundation, Frankfurt/Main</wicri:regionArea><placeName><settlement type="city">Francfort-sur-le-Main</settlement><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Darmstadt</region></placeName></affiliation></author><author><name sortKey="Rinne, Susanne" sort="Rinne, Susanne" uniqKey="Rinne S" first="Susanne" last="Rinné">Susanne Rinné</name><affiliation wicri:level="3"><nlm:affiliation>Institut für Physiologie und Pathophysiologie, Abteilung Vegetative Physiologie, Universität Marburg, 35037 Marburg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institut für Physiologie und Pathophysiologie, Abteilung Vegetative Physiologie, Universität Marburg, 35037 Marburg</wicri:regionArea><placeName><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Giessen</region><settlement type="city">Marbourg</settlement></placeName></affiliation></author><author><name sortKey="Decher, Niels" sort="Decher, Niels" uniqKey="Decher N" first="Niels" last="Decher">Niels Decher</name><affiliation wicri:level="3"><nlm:affiliation>Institut für Physiologie und Pathophysiologie, Abteilung Vegetative Physiologie, Universität Marburg, 35037 Marburg, Germany. Electronic address: decher@staff.uni-marburg.de.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institut für Physiologie und Pathophysiologie, Abteilung Vegetative Physiologie, Universität Marburg, 35037 Marburg</wicri:regionArea><placeName><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Giessen</region><settlement type="city">Marbourg</settlement></placeName></affiliation></author></analytic><series><title level="j">Molecular and cellular neurosciences</title><idno type="eISSN">1095-9327</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Action Potentials (drug effects)</term><term>Action Potentials (physiology)</term><term>Animals</term><term>Biophysics</term><term>Calcium Channel Agonists (pharmacology)</term><term>Calcium Channel Blockers (pharmacology)</term><term>Calcium Channels, L-Type (genetics)</term><term>Calcium Channels, L-Type (metabolism)</term><term>Calcium Channels, T-Type (genetics)</term><term>Calcium Channels, T-Type (metabolism)</term><term>Electric Stimulation</term><term>Green Fluorescent Proteins (genetics)</term><term>Green Fluorescent Proteins (metabolism)</term><term>In Vitro Techniques</term><term>Locus Coeruleus (cytology)</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Neurons (drug effects)</term><term>Neurons (physiology)</term><term>Patch-Clamp Techniques</term><term>Sodium Channel Blockers (pharmacology)</term><term>Statistics, Nonparametric</term><term>Tetrodotoxin (pharmacology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Calcium Channels, L-Type</term><term>Calcium Channels, T-Type</term><term>Green Fluorescent Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Calcium Channels, L-Type</term><term>Calcium Channels, T-Type</term><term>Green Fluorescent Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Calcium Channel Agonists</term><term>Calcium Channel Blockers</term><term>Sodium Channel Blockers</term><term>Tetrodotoxin</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Locus Coeruleus</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Action Potentials</term><term>Neurons</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Action Potentials</term><term>Neurons</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Biophysics</term><term>Electric Stimulation</term><term>In Vitro Techniques</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Patch-Clamp Techniques</term><term>Statistics, Nonparametric</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Dysfunction of noradrenergic locus coeruleus (LC) neurons is involved in psychiatric and neurodegenerative diseases and is an early hallmark of Parkinson's disease (PD). The analysis of ion channels underlying the autonomous electrical activity of LC neurons, which is ultimately coupled to cell survival signaling pathways, can lead to a better understanding of the vulnerability of these neurons. In LC neurons somatodendritic Ca(2+) oscillations, mediated by L-type Ca(2+) channels, accompany spontaneous spiking and are linked to mitochondrial oxidant stress. However, the expression and functional implication of low-threshold activated T-type Ca(2+) channels in LC neurons were not yet studied. To this end we performed RT-PCR expression analysis in LC neurons. In addition, we utilized slice patch clamp recordings of in vitro brainstem slices in combination with L-type and T-type Ca(2+) channel blockers. We found the expression of a distinct set of L-type and T-type Ca(2+) channel subtypes mediating a pronounced low-threshold activated Ca(2+) current component. Analyzing spike trains, we revealed that neither L-type Ca(2+) channel nor T-type Ca(2+) channel blockade alone leads to a change in firing properties. In contrast, a combined application of antagonists significantly decreased the afterhyperpolarization amplitude, resulting in an increased firing frequency. Hence, we report the functional expression of T-type Ca(2+) channels in LC neurons and demonstrate their role in increasing the robustness of LC pacemaking by working in concert with Cav1 channels.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Canada</li></country><region><li>District de Darmstadt</li><li>District de Giessen</li><li>Hesse (Land)</li></region><settlement><li>Francfort-sur-le-Main</li><li>Marbourg</li></settlement></list><tree><country name="Allemagne"><region name="Hesse (Land)"><name sortKey="Matschke, Lina A" sort="Matschke, Lina A" uniqKey="Matschke L" first="Lina A" last="Matschke">Lina A. Matschke</name></region><name sortKey="Bertoune, Mirjam" sort="Bertoune, Mirjam" uniqKey="Bertoune M" first="Mirjam" last="Bertoune">Mirjam Bertoune</name><name sortKey="Decher, Niels" sort="Decher, Niels" uniqKey="Decher N" first="Niels" last="Decher">Niels Decher</name><name sortKey="Oertel, Wolfgang H" sort="Oertel, Wolfgang H" uniqKey="Oertel W" first="Wolfgang H" last="Oertel">Wolfgang H. Oertel</name><name sortKey="Rinne, Susanne" sort="Rinne, Susanne" uniqKey="Rinne S" first="Susanne" last="Rinné">Susanne Rinné</name><name sortKey="Roeper, Jochen" sort="Roeper, Jochen" uniqKey="Roeper J" first="Jochen" last="Roeper">Jochen Roeper</name></country><country name="Canada"><noRegion><name sortKey="Snutch, Terrance P" sort="Snutch, Terrance P" uniqKey="Snutch T" first="Terrance P" last="Snutch">Terrance P. Snutch</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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