scholarly journals Cavβ surface charged residues contribute to the regulation of neuronal calcium channels

2022 ◽  
Vol 15 (1) ◽  
Author(s):  
Alexandra Tran-Van-Minh ◽  
Michel De Waard ◽  
Norbert Weiss
Keyword(s):  
Calcium Channels ◽  
Brain Function ◽  
Binding Pocket ◽  
Surface Expression ◽  
Alanine Scanning Mutagenesis ◽  
Voltage Gated Calcium Channels ◽  
Electrophysiological Recordings ◽  
Charged Residues ◽  
Direct Binding ◽  
Fine Tune

AbstractVoltage-gated calcium channels are essential regulators of brain function where they support depolarization-induced calcium entry into neurons. They consist of a pore-forming subunit (Cavα1) that requires co-assembly with ancillary subunits to ensure proper functioning of the channel. Among these ancillary subunits, the Cavβ plays an essential role in regulating surface expression and gating of the channels. This regulation requires the direct binding of Cavβ onto Cavα1 and is mediated by the alpha interacting domain (AID) within the Cavα1 subunit and the α binding pocket (ABP) within the Cavβ subunit. However, additional interactions between Cavα1 and Cavβ have been proposed. In this study, we analyzed the importance of Cavβ3 surface charged residues in the regulation of Cav2.1 channels. Using alanine-scanning mutagenesis combined with electrophysiological recordings we identified several amino acids within the Cavβ3 subunit that contribute to the gating of the channel. These findings add to the notion that additional contacts besides the main AID/ABP interaction may occur to fine-tune the expression and properties of the channel.

scholarly journals Trafficking of neuronal calcium channels

2017 ◽  
Vol 1 (1) ◽  
Author(s):  
Norbert Weiss ◽  
Gerald W. Zamponi
Keyword(s):  
Plasma Membrane ◽  
Calcium Channels ◽  
Intracellular Calcium ◽  
Dynamic Control ◽  
Surface Expression ◽  
Regulatory Mechanisms ◽  
Signalling Pathways ◽  
Physiological Functions ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels

Neuronal voltage-gated calcium channels (VGCCs) serve complex yet essential physiological functions via their pivotal role in translating electrical signals into intracellular calcium elevations and associated downstream signalling pathways. There are a number of regulatory mechanisms to ensure a dynamic control of the number of channels embedded in the plasma membrane, whereas alteration of the surface expression of VGCCs has been linked to various disease conditions. Here, we provide an overview of the mechanisms that control the trafficking of VGCCs to and from the plasma membrane, and discuss their implication in pathophysiological conditions and their potential as therapeutic targets.

scholarly journals The Participation of Microglia in Neurogenesis: A Review

2021 ◽  
Vol 11 (5) ◽  
pp. 658
Author(s):  
Diego R. Pérez-Rodríguez ◽  
Idoia Blanco-Luquin ◽  
Maite Mendioroz
Keyword(s):  
Adult Neurogenesis ◽  
Brain Function ◽  
Brain Organization ◽  
Fine Tune

Adult neurogenesis was one of the most important discoveries of the last century, helping us to better understand brain function. Researchers recently discovered that microglia play an important role in this process. However, various questions remain concerning where, at what stage, and what types of microglia participate. In this review, we demonstrate that certain pools of microglia are determinant cells in different phases of the generation of new neurons. This sheds light on how cells cooperate in order to fine tune brain organization. It also provides us with a better understanding of distinct neuronal pathologies.

scholarly journals Presynaptic Paraneoplastic Disorders of the Neuromuscular Junction: An Update

2021 ◽  
Vol 11 (8) ◽  
pp. 1035
Author(s):  
Maria Pia Giannoccaro ◽  
Patrizia Avoni ◽  
Rocco Liguori
Keyword(s):  
Potassium Channels ◽  
Neuromuscular Junction ◽  
Calcium Channels ◽  
Myasthenia Gravis ◽  
Neuromuscular Transmission ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Immune Mediated ◽  
Recent Developments ◽  
Myasthenic Syndrome

The neuromuscular junction (NMJ) is the target of a variety of immune-mediated disorders, usually classified as presynaptic and postsynaptic, according to the site of the antigenic target and consequently of the neuromuscular transmission alteration. Although less common than the classical autoimmune postsynaptic myasthenia gravis, presynaptic disorders are important to recognize due to the frequent association with cancer. Lambert Eaton myasthenic syndrome is due to a presynaptic failure to release acetylcholine, caused by antibodies to the presynaptic voltage-gated calcium channels. Acquired neuromyotonia is a condition characterized by nerve hyperexcitability often due to the presence of antibodies against proteins associated with voltage-gated potassium channels. This review will focus on the recent developments in the autoimmune presynaptic disorders of the NMJ.

scholarly journals Voltage-gated calcium channel blockers for psychiatric disorders: genomic reappraisal

2019 ◽  
Vol 216 (5) ◽  
pp. 250-253 ◽  
Author(s):  
Paul J. Harrison ◽  
Elizabeth M. Tunbridge ◽  
Annette C. Dolphin ◽  
Jeremy Hall
Keyword(s):  
Calcium Channels ◽  
Calcium Channel ◽  
Psychiatric Disorders ◽  
Calcium Channel Blockers ◽  
Channel Blockers ◽  
Risk Genes ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Voltage Gated Calcium Channel ◽  
Second Use

SummaryWe reappraise the psychiatric potential of calcium channel blockers (CCBs). First, voltage-gated calcium channels are risk genes for several disorders. Second, use of CCBs is associated with altered psychiatric risks and outcomes. Third, research shows there is an opportunity for brain-selective CCBs, which are better suited to psychiatric indications.

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