The sigma-1 receptor is a 223 amino acids molecular chaperone with a single transmembrane domain. It is resident to eukaryotic mitochondrial-associated endoplasmic reticulum and plasma membranes. By chaperone-mediated interactions with ion channels, G-protein coupled receptors and cell-signaling molecules, the sigma-1 receptor performs broad physiological and pharmacological functions. Despite sigma-1 receptors have been confirmed to regulate various types of ion channels, the relationship between the sigma-1 receptor and N-type Ca(2+) channel is still unclear. Considering both sigma-1 receptors and N-type Ca(2+) channels are involved in intracellular calcium homeostasis and neurotransmission, we undertake studies to explore the possible interaction between these two proteins. In the experiment, we confirmed the expression of the sigma-1 receptors and the N-type calcium channels in the cholinergic interneurons (ChIs) in rat striatum by using single-cell reverse transcription-polymerase chain reaction (scRT-PCR) and immunofluorescence staining. N-type Ca(2+) currents recorded from ChIs in the brain slice of rat striatum was depressed when sigma-1 receptor agonists (SKF-10047 and Pre-084) were administrated. The inhibition was completely abolished by sigma-1 receptor antagonist (BD-1063). Co-expression of the sigma-1 receptors and the N-type calcium channels in Xenopus oocytes presented a decrease of N-type Ca(2+) current amplitude with an increase of sigma-1 receptor expression. SKF-10047 could further depress N-type Ca(2+) currents recorded from oocytes. The fluorescence resonance energy transfer (FRET) assays and co-immunoprecipitation (Co-IP) demonstrated that sigma-1 receptors and N-type Ca(2+) channels formed a protein complex when they were co-expressed in HEK-293T (Human Embryonic Kidney -293T) cells. Our results revealed that the sigma-1 receptors played a negative modulation on N-type Ca(2+) channels. The mechanism for the inhibition of sigma-1 receptors on N-type Ca(2+) channels probably involved a chaperone-mediated direct interaction and agonist-induced conformational changes in the receptor-channel complexes on the cell surface.
Pharmacology, Toxicology and Pharmaceutical Science
4
17%
Neuroscience
4
17%
Medicine and Dentistry
4
17%
Biochemistry, Genetics and Molecular Biology
3
13%
Agricultural and Biological Sciences
3
13%
Other
1
4%
Unknown
4
17%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 August 2021.
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#15,462,982
of 22,977,819 outputs
Outputs from Frontiers in Pharmacology
#6,505
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Outputs of similar age
#196,926
of 313,455 outputs
Outputs of similar age from Frontiers in Pharmacology
#105
of 242 outputs
Altmetric has tracked 22,977,819 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 16,261 research outputs from this source. They receive a mean Attention Score of 5.0. This one has gotten more attention than average, scoring higher than 56% of its peers.
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We're also able to compare this research output to 242 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 54% of its contemporaries.
