21_Cav3 T-Type Voltage-Gated _ijms-23-03457-v3.pdf 1,63MB
1000 Titel
  • Cav3 T-Type Voltage-Gated Ca2+ Channels and the Amyloidogenic Environment: Pathophysiology and Implications on Pharmacotherapy and Pharmacovigilance
1000 Autor/in
  1. Papazoglou, Anna |
  2. Arshaad, Muhammad I. |
  3. Henseler, Christina |
  4. Daubner, Johanna |
  5. Broich, Karl |
  6. Hescheler, Jürgen |
  7. Ehninger, Dan |
  8. Haenisch, Britta |
  9. Weiergräber, Marco |
1000 Erscheinungsjahr 2022
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2022-03-22
1000 Erschienen in
1000 Quellenangabe
  • 23(7):3457
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2022
1000 Lizenz
1000 Verlagsversion
  • |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Voltage-gated Ca2+ channels (VGCCs) were reported to play a crucial role in neurotransmitter release, dendritic resonance phenomena and integration, and the regulation of gene expression. In the septohippocampal system, high- and low-voltage-activated (HVA, LVA) Ca2+ channels were shown to be involved in theta genesis, learning, and memory processes. In particular, HVA Cav2.3 R-type and LVA Cav3 T-type Ca2+ channels are expressed in the medial septum-diagonal band of Broca (MS-DBB), hippocampal interneurons, and pyramidal cells, and ablation of both channels was proven to severely modulate theta activity. Importantly, Cav3 Ca2+ channels contribute to rebound burst firing in septal interneurons. Consequently, functional impairment of T-type Ca2+ channels, e.g., in null mutant mouse models, caused tonic disinhibition of the septohippocampal pathway and subsequent enhancement of hippocampal theta activity. In addition, impairment of GABA A/B receptor transcription, trafficking, and membrane translocation was observed within the septohippocampal system. Given the recent findings that amyloid precursor protein (APP) forms complexes with GABA B receptors (GBRs), it is hypothesized that T-type Ca2+ current reduction, decrease in GABA receptors, and APP destabilization generate complex functional interdependence that can constitute a sophisticated proamyloidogenic environment, which could be of potential relevance in the etiopathogenesis of Alzheimer’s disease (AD). The age-related downregulation of T-type Ca2+ channels in humans goes together with increased Aβ levels that could further inhibit T-type channels and aggravate the proamyloidogenic environment. The mechanistic model presented here sheds new light on recent reports about the potential risks of T-type Ca2+ channel blockers (CCBs) in dementia, as observed upon antiepileptic drug application in the elderly.
1000 Sacherschließung
lokal pharmacoepidemiology
lokal T-type
lokal pharmacotherapy
lokal APP
lokal oscillation
lokal drugs
lokal calcium channel
lokal hippocampus
lokal septum
lokal Alzheimer’s disease
lokal interneuron
lokal GABA
lokal theta
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
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  1. Bundesinstitut für Arzneimittel und Medizinprodukte |
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    1000 Förderer Bundesinstitut für Arzneimittel und Medizinprodukte |
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1000 Erstellt am 2022-04-04T12:53:18.266+0200
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