journal
https://read.qxmd.com/read/38354101/recent-advances-on-the-structure-and-the-function-relationships-of-the-trpv4-ion-channel
#1
REVIEW
Raúl Sánchez-Hernández, Miguel Benítez-Angeles, Ana M Hernández-Vega, Tamara Rosenbaum
The members of the superfamily of Transient Receptor Potential (TRP) ion channels are physiologically important molecules that have been studied for many years and are still being intensively researched. Among the vanilloid TRP subfamily, the TRPV4 ion channel is an interesting protein due to its involvement in several essential physiological processes and in the development of various diseases. As in other proteins, changes in its function that lead to the development of pathological states, have been closely associated with modification of its regulation by different molecules, but also by the appearance of mutations which affect the structure and gating of the channel...
December 2024: Channels
https://read.qxmd.com/read/38184795/a-phenylalanine-at-the-extracellular-side-of-kir1-1-facilitates-potassium-permeation
#2
JOURNAL ARTICLE
Henry Sackin, Mikheil Nanazashvili
The Kir1.1 (ROMK) family of weak inward rectifiers controls K secretion in the renal CCT and K recycling in the renal TALH. A single point mutant of the inward rectifier, F127V-Kir1.1b was used to investigate the K transition between the selectivity filter and the outer mouth of the channel. We hypothesize that normally an aromatic Phe at the external entryway of Kir1.1b facilitates outward K secretion. We tested this by replacing F127-Kir1.1b with a small aliphatic Val . Results indicate that removal of the Phe at 127 suppresses outward currents that normally contribute to K secretion...
December 2024: Channels
https://read.qxmd.com/read/38154061/reducing-agents-facilitate-membrane-patch-seal-integrity-and-longevity
#3
JOURNAL ARTICLE
Damayantee Das, Anson Wong, Timothy N Friedman, Bradley J Kerr, Harley T Kurata, Shawn M Lamothe
The patch clamp method is a widely applied electrophysiological technique used to understand ion channel activity and cellular excitation. The formation of a high resistance giga-ohm seal is required to obtain high-quality recordings but can be challenging due to variables including operator experience and cell preparation. Therefore, the identification of methods to promote the formation and longevity of giga-ohm seals may be beneficial. In this report, we describe our observation that the application of reducing agents (DTT and TCEP) to the external bath solution during whole-cell patch clamp recordings of heterologous cells (HEK and LM) and cultured primary cells (DRG neurons) enhanced the success of giga-ohm seal formation...
December 2024: Channels
https://read.qxmd.com/read/38154047/novel-insights-into-voltage-gated-ion-channels-translational-breakthroughs-in-medical-oncology
#4
JOURNAL ARTICLE
Minas Sakellakis, Sung Mi Yoon, Jashan Reet, Athanasios Chalkias
Preclinical evidence suggests that voltage gradients can act as a kind of top-down master regulator during embryogenesis and orchestrate downstream molecular-genetic pathways during organ regeneration or repair. Moreover, electrical stimulation shifts response to injury toward regeneration instead of healing or scarring. Cancer and embryogenesis not only share common phenotypical features but also commonly upregulated molecular pathways. Voltage-gated ion channel activity is directly or indirectly linked to the pathogenesis of cancer hallmarks, while experimental and clinical studies suggest that their modulation, e...
December 2024: Channels
https://read.qxmd.com/read/38062897/structural-biology-of-voltage-gated-calcium-channels
#5
REVIEW
Xia Yao, Shuai Gao, Nieng Yan
Voltage-gated calcium (Cav ) channels mediate Ca2+ influx in response to membrane depolarization, playing critical roles in diverse physiological processes. Dysfunction or aberrant regulation of Cav channels can lead to life-threatening consequences. Cav -targeting drugs have been clinically used to treat cardiovascular and neuronal disorders for several decades. This review aims to provide an account of recent developments in the structural dissection of Cav channels. High-resolution structures have significantly advanced our understanding of the working and disease mechanisms of Cav channels, shed light on the molecular basis for their modulation, and elucidated the modes of actions (MOAs) of representative drugs and toxins...
December 2024: Channels
https://read.qxmd.com/read/38055732/sodium-currents-in-na%C3%A3-ve-mouse-dorsal-root-ganglion-neurons-no-major-differences-between-sexes
#6
JOURNAL ARTICLE
Mohammad-Reza Ghovanloo, Sidharth Tyagi, Peng Zhao, Philip R Effraim, Sulayman D Dib-Hajj, Stephen G Waxman
Sexual dimorphism has been reported in multiple pre-clinical and clinical studies on pain. Previous investigations have suggested that in at least some states, rodent dorsal root ganglion (DRG) neurons display differential sex-dependent regulation and expression patterns of various proteins involved in the pain pathway. Our goal in this study was to determine whether sexual dimorphism in the biophysical properties of voltage-gated sodium (Nav) currents contributes to these observations in rodents. We recently developed a novel method that enables high-throughput, unbiased, and automated functional analysis of native rodent sensory neurons from naïve WT mice profiled simultaneously under uniform experimental conditions...
December 2024: Channels
https://read.qxmd.com/read/38033122/a-structural-atlas-of-druggable-sites-on-na-v-channels
#7
JOURNAL ARTICLE
Zhangqiang Li, Qiurong Wu, Nieng Yan
Voltage-gated sodium (Nav ) channels govern membrane excitability by initiating and propagating action potentials. Consistent with their physiological significance, dysfunction, or mutations in these channels are associated with various channelopathies. Nav channels are thereby major targets for various clinical and investigational drugs. In addition, a large number of natural toxins, both small molecules and peptides, can bind to Nav channels and modulate their functions. Technological breakthrough in cryo-electron microscopy (cryo-EM) has enabled the determination of high-resolution structures of eukaryotic and eventually human Nav channels, alone or in complex with auxiliary subunits, toxins, and drugs...
December 2024: Channels
https://read.qxmd.com/read/37983307/voltage-gated-sodium-and-calcium-channels-discovery-structure-function-and-pharmacology
#8
REVIEW
William A Catterall
Voltage-gated sodium channels initiate action potentials in nerve and muscle, and voltage-gated calcium channels couple depolarization of the plasma membrane to intracellular events such as secretion, contraction, synaptic transmission, and gene expression. In this Review and Perspective article, I summarize early work that led to identification, purification, functional reconstitution, and determination of the amino acid sequence of the protein subunits of sodium and calcium channels and showed that their pore-forming subunits are closely related...
December 2023: Channels
https://read.qxmd.com/read/37983306/transient-receptor-potential-vanilloid-type-1-cardioprotective-effects-in-diabetic-models
#9
REVIEW
Jiaqi Bao, Zhicheng Gao, Yilan Hu, Lifang Ye, Lihong Wang
Cardiovascular disease, especially heart failure (HF) is the leading cause of death in patients with diabetes. Individuals with diabetes are prone to a special type of cardiomyopathy called diabetic cardiomyopathy (DCM), which cannot be explained by heart diseases such as hypertension or coronary artery disease, and can contribute to HF. Unfortunately, the current treatment strategy for diabetes-related cardiovascular complications is mainly to control blood glucose levels; nonetheless, the improvement of cardiac structure and function is not ideal...
December 2023: Channels
https://read.qxmd.com/read/37934721/a-systemic-analysis-of-monocarboxylate-transporters-in-ovarian-cancer-and-possible-therapeutic-interventions
#10
JOURNAL ARTICLE
Priti Chatterjee, Debaleena Bhowmik, Sib Sankar Roy
Monocarboxylate transporters (MCTs) play an immense role in metabolically active solid tumors by regulating concentration-dependent transport of different important monocarboxylates including pyruvate and lactate and are encoded by the SLC16A family of genes. Given the vast array of functions, these transporters play in oncogenesis, our objective was to look into the association of MCT1 (SLC16A1), MCT2 (SLC16A7), MCT3 (SLC16A8), and MCT4 (SLC16A3) with Epithelial ovarian cancer (EOC) pathophysiology by exploiting various publicly available databases and web resources...
December 2023: Channels
https://read.qxmd.com/read/37905307/structural-basis-of-properties-mechanisms-and-channelopathy-of-cyclic-nucleotide-gated-channels
#11
REVIEW
Zhengshan Hu, Jian Yang
Recent years have seen an outpouring of atomic or near atomic resolution structures of cyclic nucleotide-gated (CNG) channels, captured in closed, transition, pre-open, partially open, and fully open states. These structures provide unprecedented molecular insights into the activation, assembly, architecture, regulation, and channelopathy of CNG channels, as well as mechanistic explanations for CNG channel biophysical and pharmacological properties. This article summarizes recent advances in CNG channel structural biology, describes key structural features and elements, and illuminates a detailed conformational landscape of activation by cyclic nucleotides...
December 2023: Channels
https://read.qxmd.com/read/37905302/the-role-of-atp-binding-cassette-abc-transporters-in-breast-cancer-evaluating-prognosis-predicting-immunity-and-guiding-treatment
#12
JOURNAL ARTICLE
Yuan Yuan, Zhouhong Xiang, Yuhua Xia, Jiaheng Xie, Xiudi Jiang, Zhicheng Lu
Breast cancer is currently the most prevalent form of cancer worldwide. Nevertheless, there remains limited clarity regarding our understanding of the tumor microenvironment and metabolic characteristics associated with it. ATP-binding cassette (ABC) transporters are the predominant transmembrane transporters found in organisms. Therefore, it is essential to investigate the role of ABC transporters in breast cancer. Transcriptome data from breast cancer patients were downloaded from the TCGA database. ABC transporter-related genes were obtained from the Genecards database...
December 2023: Channels
https://read.qxmd.com/read/37838981/molecular-pharmacology-of-the-onco-trp-channel-trpv6
#13
REVIEW
Arthur Neuberger, Alexander I Sobolevsky
TRPV6, a representative of the vanilloid subfamily of TRP channels, serves as the principal calcium uptake channel in the gut. Dysregulation of TRPV6 results in disturbed calcium homeostasis leading to a variety of human diseases, including many forms of cancer. Inhibitors of this oncochannel are therefore particularly needed. In this review, we provide an overview of recent advances in structural pharmacology that uncovered the molecular mechanisms of TRPV6 inhibition by a variety of small molecules, including synthetic and natural, plant-derived compounds as well as some prospective and clinically approved drugs...
December 2023: Channels
https://read.qxmd.com/read/37818548/type-3-ip3-receptor-its-structure-functions-and-related-disease-implications
#14
REVIEW
Lvying Wu, Jin Chen
Cell-fate decisions depend on the precise and strict regulation of multiple signaling molecules and transcription factors, especially intracellular Ca2+ homeostasis and dynamics. Type 3 inositol 1,4,5-triphosphate receptor (IP3R3) is an a tetrameric channel that can mediate the release of Ca2+ from the endoplasmic reticulum (ER) in response to extracellular stimuli. The gating of IP3R3 is regulated not only by ligands but also by other interacting proteins. To date, extensive research conducted on the basic structure of IP3R3, as well as its regulation by ligands and interacting proteins, has provided novel perspectives on its biological functions and pathogenic mechanisms...
December 2023: Channels
https://read.qxmd.com/read/37807670/overlap-in-synaptic-neurological-condition-susceptibility-pathways-and-the-neural-pannexin-1-interactome-revealed-by-bioinformatics-analyses
#15
JOURNAL ARTICLE
Simona D Frederiksen, Leigh E Wicki-Stordeur, Leigh Anne Swayne
Many neurological conditions exhibit synaptic impairments, suggesting mechanistic convergence. Additionally, the pannexin 1 (PANX1) channel and signaling scaffold is linked to several of these neurological conditions and is an emerging regulator of synaptic development and plasticity; however, its synaptic pathogenic contributions are relatively unexplored. To this end, we explored connections between synaptic neurodevelopmental disorder and neurodegenerative disease susceptibility genes discovered by genome-wide association studies (GWASs), and the neural PANX1 interactome (483 proteins) identified from mouse Neuro2a (N2a) cells...
December 2023: Channels
https://read.qxmd.com/read/37695839/structure-of-the-voltage-gated-potassium-channel-k-v-1-3-insights-into-the-inactivated-conformation-and-binding-to-therapeutic-leads
#16
REVIEW
K George Chandy, Karoline Sanches, Raymond S Norton
The voltage-gated potassium channel KV 1.3 is an important therapeutic target for the treatment of autoimmune and neuroinflammatory diseases. The recent structures of KV 1.3, Shaker-IR (wild-type and inactivating W434F mutant) and an inactivating mutant of rat KV 1.2-KV 2.1 paddle chimera (KV Chim-W362F+S367T+V377T) reveal that the transition of voltage-gated potassium channels from the open-conducting conformation into the non-conducting inactivated conformation involves the rupture of a key intra-subunit hydrogen bond that tethers the selectivity filter to the pore helix...
December 2023: Channels
https://read.qxmd.com/read/37523628/tmem120a-tacan-a-putative-regulator-of-ion-channels-mechanosensation-and-lipid-metabolism
#17
REVIEW
Matthew Gabrielle, Tibor Rohacs
TMEM120A (TACAN) is an enigmatic protein with several seemingly unconnected functions. It was proposed to be an ion channel involved in sensing mechanical stimuli, and knockdown/knockout experiments have implicated that TMEM120A may be necessary for sensing mechanical pain. TMEM120A's ion channel function has subsequently been challenged, as attempts to replicate electrophysiological experiments have largely been unsuccessful. Several cryo-EM structures revealed TMEM120A is structurally homologous to a lipid modifying enzyme called Elongation of Very Long Chain Fatty Acids 7 (ELOVL7)...
December 2023: Channels
https://read.qxmd.com/read/37463317/advancements-in-the-study-of-inward-rectifying-potassium-channels-on-vascular-cells
#18
REVIEW
Chunshu Li, Yan Yang
Inward rectifier potassium channels (Kir channels) exist in a variety of cells and are involved in maintaining resting membrane potential and signal transduction in most cells, as well as connecting metabolism and membrane excitability of body cells. It is closely related to normal physiological functions of body and the occurrence and development of some diseases. Although the functional expression of Kir channels and their role in disease have been studied, they have not been fully elucidated. In this paper, the functional expression of Kir channels in vascular endothelial cells and smooth muscle cells and their changes in disease states were reviewed, especially the recent research progress of Kir channels in stem cells was introduced, in order to have a deeper understanding of Kir channels in vascular tissues and provide new ideas and directions for the treatment of related ion channel diseases...
December 2023: Channels
https://read.qxmd.com/read/37389974/secretory-carrier-associated-membrane-protein-5-regulates-cell-surface-targeting-of-t-type-calcium-channels
#19
JOURNAL ARTICLE
Emilio R Mustafá, Konstantin Weiß, Norbert Weiss
Missense mutations in the human secretary carrier-associated membrane protein 5 (SCAMP5) cause a variety of neurological disorders including neurodevelopmental delay, epilepsy, and Parkinson's disease. We recently documented the importance of SCAMP2 in the regulation of T-type calcium channel expression in the plasma membrane. Here, we show that similar to SCAMP2, the co-expression of SCAMP5 in tsA-201 cells expressing recombinant Cav 3.1, Cav 3.2, and Cav 3.3 channels nearly abolished whole-cell T-type currents...
December 2023: Channels
https://read.qxmd.com/read/37243715/cycling-matters-sex-hormone-regulation-of-vascular-potassium-channels
#20
REVIEW
Samuel N Baldwin, Thomas A Jepps, Iain A Greenwood
Sex hormones and the reproductive cycle (estrus in rodents and menstrual in humans) have a known impact on arterial function. In spite of this, sex hormones and the estrus/menstrual cycle are often neglected experimental factors in vascular basic preclinical scientific research. Recent research by our own laboratory indicates that cyclical changes in serum concentrations of sex -hormones across the rat estrus cycle, primary estradiol, have significant consequences for the subcellular trafficking and function of KV ...
December 2023: Channels
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