scholarly journals Nanoenviroments of the β-Subunit of L-Type Voltage-Gated Calcium Channels in Adult Cardiomyocytes

2022 ◽  
Vol 9 ◽  
Author(s):  
Yiliam Cruz-Garcia ◽  
Katalin Barkovits ◽  
Michael Kohlhaas ◽  
Simone Pickel ◽  
Michelle Gulentz ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Cardiac Contraction ◽  
Release Mechanism ◽  
Cellular Functions ◽  
Excitation Contraction Coupling ◽  
Voltage Gated ◽  
Contraction Coupling ◽  
Voltage Gated Calcium Channels ◽  
Adult Cardiomyocytes ◽  
Src Homology

In cardiomyocytes, Ca2+ influx through L-type voltage-gated calcium channels (LTCCs) following membrane depolarization regulates crucial Ca2+-dependent processes including duration and amplitude of the action potentials and excitation-contraction coupling. LTCCs are heteromultimeric proteins composed of the Cavα1, Cavβ, Cavα2δ and Cavγ subunits. Here, using ascorbate peroxidase (APEX2)-mediated proximity labeling and quantitative proteomics, we identified 61 proteins in the nanoenvironments of Cavβ2 in cardiomyocytes. These proteins are involved in diverse cellular functions such as cellular trafficking, cardiac contraction, sarcomere organization and excitation-contraction coupling. Moreover, pull-down assays and co-immunoprecipitation analyses revealed that Cavβ2 interacts with the ryanodine receptor 2 (RyR2) in adult cardiomyocytes, probably coupling LTCCs and the RyR2 into a supramolecular complex at the dyads. This interaction is mediated by the Src-homology 3 domain of Cavβ2 and is necessary for an effective pacing frequency-dependent increase of the Ca2+-induced Ca2+ release mechanism in cardiomyocytes.

Cardiac excitation-contraction coupling: role of membrane potential in regulation of contraction

2001 ◽  
Vol 280 (5) ◽  
pp. H1928-H1944 ◽  
Author(s):  
Gregory R. Ferrier ◽  
Susan E. Howlett
Keyword(s):  
Membrane Potential ◽  
Regulatory Mechanism ◽  
Cardiac Contraction ◽  
Release Mechanism ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Regulation Of Contraction ◽  
Cardiac Excitation ◽  
The Impact

The steps that couple depolarization of the cardiac cell membrane to initiation of contraction remain controversial. Depolarization triggers a rise in intracellular free Ca2+ which activates contractile myofilaments. Most of this Ca2+ is released from the sarcoplasmic reticulum (SR). Two fundamentally different mechanisms have been proposed for SR Ca2+ release: Ca2+-induced Ca2+ release (CICR) and a voltage-sensitive release mechanism (VSRM). Both mechanisms operate in the same cell and may contribute to contraction. CICR couples the release of SR Ca2+ closely to the magnitude of the L-type Ca2+ current. In contrast, the VSRM is graded by membrane potential rather than Ca2+ current. The electrophysiological and pharmacological characteristics of the VSRM are strikingly different from CICR. Furthermore, the VSRM is strongly modulated by phosphorylation and provides a new regulatory mechanism for cardiac contraction. The VSRM is depressed in heart failure and may play an important role in contractile dysfunction. This review explores the operation and characteristics of the VSRM and CICR and discusses the impact of the VSRM on our understanding of cardiac excitation-contraction coupling.

scholarly journals The Src Homology 3 Domain of the β-Subunit of Voltage-gated Calcium Channels Promotes Endocytosis via Dynamin Interaction

2006 ◽  
Vol 282 (4) ◽  
pp. 2156-2162 ◽  
Author(s):  
Giovanni Gonzalez-Gutierrez ◽  
Erick Miranda-Laferte ◽  
Alan Neely ◽  
Patricia Hidalgo
Keyword(s):  
Calcium Channels ◽  
Β Subunit ◽  
Voltage Gated ◽  
Src Homology 3 ◽  
Voltage Gated Calcium Channels ◽  
Src Homology 3 Domain ◽  
Src Homology

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.

Appearance of voltage-gated calcium channels following overexpression of ATPase II cDNA in neuronal HN2 cells

2003 ◽  
Vol 117 (2) ◽  
pp. 109-115 ◽  
Author(s):  
Gary Chin ◽  
Yasir El-Sherif ◽  
Farah Jayman ◽  
Rima Estephan ◽  
Andrzej Wieraszko ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Atpase Ii
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