1. A combined biochemical and electrophysiological approach was used to determine the mechanism by which the auxiliary subunits of Ca2+ channel enhance the macroscopic Ca2+ currents. Xenopus oocytes were injected with RNA of the main pore-forming subunit (cardiac: alpha 1C), and various combinations of RNAs of the auxiliary subunits (alpha 2/delta and beta 2A). 2. The single channel open probability (Po; measured at 0 mV) was increased approximately 3-, approximately 8- and approximately 35-fold by alpha 2/delta, beta 2A and alpha 2/delta+beta 2A, respectively. The whole-cell Ca2+ channel current was increased approximately 8- to 10-fold by either alpha 2/delta or beta 2A, and synergistically > 100-fold by alpha 2/delta+beta 2A. The amount of 35S-labelled alpha 1 protein in the plasma membrane was not changed by coexpression of beta 2A, but was tripled by coexpression of alpha 2/delta (either with or without beta). 3. We conclude that the increase in macroscopic current by alpha 2/delta is equally due to changes in amount of alpha 1 in the plasma membrane and an increase in Po, whereas all of the effect of beta 2A is due to an increase in Po. The synergy between alpha 2/delta and beta in increasing the macroscopic current is due mainly to synergistic changes in channel gating.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1156791 | PMC |
| http://dx.doi.org/10.1113/jphysiol.1995.sp021029 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Autism-Linked Mutations in αδ-1 and αδ-3 Reduce Protein Membrane Expression but Affect Neither Calcium Channels nor Trans-Synaptic Signaling.
Pharmaceuticals (Basel)
November 2024
Division of Physiology, Department of Pharmacology, Physiology, and Microbiology, Karl Landsteiner University of Health Sciences, 3500 Krems, Austria.
Background: αδ proteins regulate membrane trafficking and biophysical properties of voltage-gated calcium channels. Moreover, they modulate axonal wiring, synapse formation, and trans-synaptic signaling. Several rare missense variants in CACNA2D1 (coding for αδ-1) and CACNA2D3 (coding for αδ-3) genes were identified in patients with autism spectrum disorder (ASD).
View Article and Find Full Text PDFAutotrophic ammonium nitrogen removal process mediated by manganese oxides: Bioreactors performance optimization and potential mechanisms.
Environ Res
January 2025
School of Environmental and Municipal Engineering, Xi'an University of Architecture and Technology, Xi'an 710055, China; Shaanxi Key Laboratory of Environmental Engineering, Xi'an University of Architecture and Technology, Xi'an 710055, China.
Manganese(IV) (Mn(IV)) reduction coupled with ammonium (NH-N) oxidation (Mnammox) has been found to play a significant role in the nitrogen (N) cycle within natural ecosystems. However, research and application of the autotrophic NH-N removal process mediated by manganese oxides (MnOx) in wastewater treatment are currently limited. This study established autotrophic NH-N removal sludge reactors mediated by various MnOx types, including δ-MnO (δ-MSR), β-MnO (β-MSR), α-MnO (α-MSR), and natural Mn ore (MOSR), investigating their NH-N removal performances and mechanisms under different initial N loading and pH conditions.
View Article and Find Full Text PDFTandospirone prevents anesthetic-induced respiratory depression through 5-HT receptor activation in rats.
Sci Rep
January 2025
Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Taiping Road 27, Beijing, 100850, China.
Respiratory depression is a side effect of anesthetics. Treatment with specific antagonists or respiratory stimulants can reverse respiratory depression caused by anesthetics; however, they also interfere with the sedative effects of anesthetics. Previous studies have suggested that tandospirone may ameliorate respiratory depression without affecting the sedative effects of anesthetics.
View Article and Find Full Text PDFTNF-α exacerbates SARS-CoV-2 infection by stimulating CXCL1 production from macrophages.
PLoS Pathog
December 2024
Division of Viral Infection, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Since most genetically modified mice are C57BL/6 background, a mouse-adapted SARS-CoV-2 that causes lethal infection in young C57BL/6 mice is useful for studying innate immune protection against SARS-CoV-2 infection. Here, we established two mouse-adapted SARS-CoV-2, ancestral and Delta variants, by serial passaging 80 times in C57BL/6 mice. Although young C57BL/6 mice were resistant to infection with the mouse-adapted ancestral SARS-CoV-2, the mouse-adapted SARS-CoV-2 Delta variant caused lethal infection in young C57BL/6 mice.
View Article and Find Full Text PDFMirogabalin as a novel calcium channel αδ ligand for the treatment of neuropathic pain: a review of clinical update.
Front Pharmacol
November 2024
Department of Neurology, The First Medical Center, Chinese PLA General Hospital, Beijing, China.
Neuropathic pain (NP) is often caused by diabetic neuropathy, chemotherapy, or spinal cord lesions and is associated with significant economic burden and poor quality of life. Sophisticated etiology and pathology recognized different pharmacologic interventions, and hitherto, the reported analgesic efficacy and safety of guideline-recommended drugs are not satisfactory. Overall, this article reviews the mechanism of αδ ligand, the clinical pharmacokinetics, efficacy, safety and cost-effectiveness of mirogabalin for the treatment of NP, offering clinical perspectives into potential benefits of NP-related syndrome or comorbidities.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!