Article
Biochemistry & Molecular Biology
Stefano Stabilini, Anna Menini, Simone Pifferi
Summary: TMEM16F is involved in various physiological processes and acts as both a Ca2+-dependent phospholipid scramblase and a Ca2+-activated ion channel. The ion selectivity of TMEM16F-mediated current depends on the recording configuration, with higher permeability for Na+ in inside-out experiments and a slight preference for Cl over bar permeation in whole-cell recordings.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Hang Zhang, Shiyu Wang, Zhenzhen Zhang, Mengzhuo Hou, Chunyu Du, Zhenye Zhao, Horst Vogel, Zhifang Li, Kaige Yan, Xiaokang Zhang, Jianping Lu, Yujie Liang, Shuguang Yuan, Daping Wang, Huawei Zhang
Summary: Pannexin 2 plays critical roles in many physiological processes but its mechanism remains unclear. In this study, the cryo-EM structure of human Panx2 in the open state is reported, and critical residues for its gating are identified.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Qiang Liu, Jin Wang, Xin Wei, Juan Hu, Conghui Ping, Yue Gao, Chang Xie, Peiyu Wang, Peng Cao, Zhengyu Cao, Ye Yu, Dongdong Li, Jing Yao
Summary: The study found that the clinical medication dyclonine can inhibit the TRPV3 channel, rescuing cell death caused by gain-of-function mutations and suppressing itch symptoms in a mouse model. By molecular simulations and mutagenesis, key residues in the TRPV3 pore region were identified that could affect the inhibitory efficiency of dyclonine.
Article
Multidisciplinary Sciences
Johann Biedermann, Sebastian Braunbeck, Andrew J. R. Plested, Han Sun
Summary: Fast excitatory synaptic transmission in the central nervous system relies on the AMPA-type glutamate receptor (AMPAR), which incorporates a nonselective cation channel. Recent studies combining molecular dynamic simulations and electrophysiology have revealed the ion permeation mechanisms of AMPA receptors, showing that Na+, K+, and Cs+ can permeate at physiological rates through a simple selectivity filter structure. The permissive architecture of the filter allows for rapid, nonselective cation permeation and copermeation by water, with Cs+ slightly more permeant than Na+ due to preferential binding sites.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biology
Christian J. G. Tessier, Raymond M. Sturgeon, Johnathon R. Emlaw, Gregory D. McCluskey, F. Javier Perez-Areales, Corrie J. B. daCosta
Summary: Human adult muscle-type acetylcholine receptors are heteropentameric ion channels formed from different subunits, but they share a common ancestral homopentameric origin. A reconstructed ancestral muscle-type beta-subunit can form spontaneously open homopentameric ion channels, demonstrating that the function of the receptor is independent of agonist and does not require complex heteropentameric architecture.
Article
Biochemistry & Molecular Biology
Hao Li, Wang Jiang, Shi-Rong Zhang, Peng-Cheng Li, Tian-Jiao Li, Wei Jin, Hua-Xiang Xu, Xian-Jun Yu, Liang Liu
Summary: This study found that CD41+/CD62P+ platelets are closely associated with the prognosis of pancreatic ductal adenocarcinoma (PDAC). High levels of CD41+/CD62P+ platelets were correlated with microvascular invasion, advanced AJCC stage, and high CA19-9 level, and independently predicted a poor prognosis for resectable PDAC. Mechanistically, Panx1 in CD41+/CD62P+ platelets promotes PDAC cell invasion and metastasis by enhancing IL-1 beta secretion through the phosphorylation of p38 MAPK. In addition, a novel compound named PC63435 was synthesized, which blocked the Panx1/IL-1 beta pathway and reduced the proportion of CD41+/CD62P+ platelets, leading to the suppression of PDAC tumor invasion and metastasis.
Article
Pharmacology & Pharmacy
Michael Koval, Wyatt J. Schug, Brant E. Isakson
Summary: Pannexin channels have important roles in regulating inflammation and are associated with various diseases. Blocking these channels pharmacologically is crucial for therapeutic approaches. This review discusses the current state of agents that can block pannexin channels, focusing on pharmaceuticals and peptide mimetics targeting pannexin 1. It also provides guidance on interpreting results obtained with pannexin pharmacologics and evaluates the strengths and limitations of different agents in terms of specificity and clinical application.
CURRENT OPINION IN PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Arthur Neuberger, Mai Oda, Yury A. Nikolaev, Kirill D. Nadezhdin, Elena O. Gracheva, Sviatoslav N. Bagriantsev, Alexander I. Sobolevsky
Summary: Small molecules targeting transient receptor potential (TRP) channels have the potential to control pain. This study reports the cryo-EM structures of human TRPV1 in the absence of ligands or in the presence of the TRPV1-specific antagonist SB-366791, providing insights for the design of new promising analgesic drugs.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Caroline Hempel, Rita Rosenthal, Anja Fromm, Susanne M. Krug, Michael Fromm, Dorothee Gunzel, Joerg Piontek
Summary: This study analyzed the structural and functional differences between claudin-15 and claudin-10b cation channels and identified several mutants that affect ion permeability and pore diameter. Furthermore, the study revealed that the charge at the W63/K64 position has an impact on the assembly and properties of claudin-10b channels but not claudin-15 channels.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2022)
Article
Spectroscopy
Jingjie Yu, Yifei Xu, Shikao Shi, Jiye Wang, Huihua Song, Lianshe Fu
Summary: This paper reports the fabrication of a novel Tb3+ activated layered lutetium hydroxide and the tuning of its structure and spectroscopic properties through ion-exchange and intercalation of organic molecules. The hybrid material exhibited enhanced fluorescence emission and excellent stability, making it a highly potential sensor for the detection of Cu2+ ions.
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
(2022)
Article
Multidisciplinary Sciences
Kazuki Okamoto, Teppei Ebina, Naoki Fujii, Kuniaki Konishi, Yu Sato, Tetsuhiko Kashima, Risako Nakano, Hiroyuki Hioki, Haruki Takeuchi, Junji Yumoto, Masanori Matsuzaki, Yuji Ikegaya
Summary: The newly introduced Tb3+-doped glass material emits green fluorescence in biological experiments and is compatible with conventional research environments. Using micropipettes made of Tb3+-doped glass allows for various operations on GFP-labeled cells under real-time fluorescence microscopic control.
Article
Neurosciences
Xiao-Li Mao, Yi-Xuan Chen, Huan Yu, Quan-Wei Yang
Summary: Eugenol concentration-dependently inhibited ASIC currents in TG neurons in a non-competitive and G-protein independent manner, suggesting that ASICs could be a molecular target for eugenol in TG neurons. Eugenol also partly inhibited ASIC3 currents in CHO cells transfected with ASIC3. These findings contribute to a better understanding of the analgesic effect of eugenol in dental treatment.
NEUROSCIENCE LETTERS
(2023)
Review
Cell Biology
Kirk a Taylor, Gemma Little, Jonathan M. Gibbins
Summary: Connexins and Pannexins are families of proteins expressed widely in mammalian cells, forming channels that play a role in intercellular signaling. In platelets, pannexin-1 and connexins are involved in non-vesicular ATP release and have the potential to be drug targets for arterial thrombosis management, as their activation is regulated by physiological stimuli such as mechanical stimulation.
Article
Cell Biology
Gregory C. Amberg, Ji Yeon Lee, Sang Don Koh, Kenton M. Sanders
Summary: A-type currents, rapidly inactivating voltage-gated potassium currents, were identified in smooth muscle cells (SMCs) isolated from murine fundus, with robust peak amplitudes averaging 1.5 nA at 0 mV. These currents are likely active at physiological membrane potentials and contribute to the negative membrane potentials of this tonic smooth muscle. Kv4 channels are likely responsible for generating the A-type current in murine fundus SMCs, as confirmed by quantitative analysis and immunohistochemistry.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2021)
Article
Microbiology
Ulrike Breitinger, Nourhan K. M. Ali, Heinrich Sticht, Hans-Georg Breitinger
Summary: Research on the SARS-CoV envelope protein E has revealed its involvement in various aspects of the virus life cycle. The study of channel activity and viroporin inhibitors provides valuable insights for the development of novel antiviral drugs to suppress virus activity and proliferation.
FRONTIERS IN MICROBIOLOGY
(2021)
Review
Physiology
Morten S. Nielsen, Chantal J. M. van Opbergen, Toon A. B. van Veen, Mario Delmar
Summary: The intercalated disc (ID) is a specialized structure that connects cardiomyocytes via mechanical and electrical junctions. Recent studies have revealed the complex nanostructure and molecular composition of the ID, highlighting the fact that it is not just a simple cell-to-cell coupling junction but rather an interacting molecular complex. Understanding the physiological implications of the ID architecture and the local intermolecular interactions is crucial for understanding normal cardiac conduction and the pathophysiology of arrhythmias.
PHYSIOLOGICAL REVIEWS
(2023)
Article
Neurosciences
Nina Rostgaard, Markus Harboe Olsen, Maud Ottenheijm, Lylia Drici, Anja Hviid Simonsen, Peter Plomgaard, Hanne Gredal, Helle Harding Poulsen, Henrik Zetterberg, Kaj Blennow, Steen Gregers Hasselbalch, Nanna MacAulay, Marianne Juhler
Summary: This study aimed to compare the molecular composition of cerebrospinal fluid (CSF) obtained from the ventricular and the lumbar compartments and evaluate the feasibility of using lumbar CSF as a proxy for ventricular CSF. Results showed differences in protein composition and distribution of clinically employed biomarkers between the two compartments. However, for certain proteins and biomarkers, lumbar CSF can be reliably used as a proxy for ventricular CSF if a lumbar/cranial index has been established. It is important to verify the compartmental preference before extrapolating from lumbar CSF to ventricular fluid.
FLUIDS AND BARRIERS OF THE CNS
(2023)
Article
Biology
Georgia Balsevich, Gavin N. Petrie, Daniel E. Heinz, Arashdeep Singh, Robert J. Aukema, Avery C. Hunker, Haley A. Vecchiarelli, Hiulan Yau, Martin Sticht, Roger J. Thompson, Francis S. Lee, Larry S. Zweifel, Prasanth K. Chelikani, Nils C. Gassen, Matthew N. Hill
Summary: A study found that the impact of FAAH C385A on metabolic outcomes is influenced by the environmental context. This genotype amplifies orexigenic responses and decreases anorexigenic responses, providing a potential explanation for the conflicting findings in previous human studies.
Article
Neurosciences
Pooya Razzaghi Khamesi, Vasileios Charitatos, Eva K. K. Heerfordt, Nanna MacAulay, Vartan Kurtcuoglu
Summary: A computational model was developed to examine the role of the standing osmotic gradient mechanism in cerebrospinal fluid (CSF) production by the ventricular choroid plexus (ChP). The model suggests that the standing osmotic gradients have minimal effect on CSF production and are unlikely to be the main drivers.
FLUIDS AND BARRIERS OF THE CNS
(2023)
Article
Neurosciences
Jonathan H. Wardman, Mette N. Jensen, Soren N. Andreassen, Bjarne Styrishave, Jens E. Wilhjelm, Alexandra J. Sinclair, Nanna MacAulay
Summary: Idiopathic intracranial hypertension (IIH) is characterized by increased intracranial pressure, impaired vision, and headache. This study investigated the role of obesity and hormonal perturbations in IIH pathophysiology using rat models. The results suggest that obesity-induced androgen dysregulation may contribute to the disease mechanism of IIH.
FLUIDS AND BARRIERS OF THE CNS
(2023)
Article
Neurosciences
Annette Buur Steffensen, Beatriche Louise Edelbo, Dagne Barbuskaite, Soren Norge Andreassen, Markus Harboe Olsen, Kirsten Moller, Nanna MacAulay
Summary: Maintaining intracranial pressure (ICP) within the physiological range is crucial for proper brain function. Fluctuations in ICP during the light-dark phase cycle may complicate diagnosis and treatment choice for patients with pressure-related disorders. These fluctuations are likely caused by circadian or sleep-wake cycle-mediated modulation of cerebrospinal fluid (CSF) flow dynamics, which may also play a role in diurnal regulation of brain waste clearance.
FLUIDS AND BARRIERS OF THE CNS
(2023)
Article
Biochemistry & Molecular Biology
Nina Rostgaard, Markus Harboe Olsen, Tenna Capion, Nanna MacAulay, Marianne Juhler
Summary: This study aimed to identify inflammatory biomarkers in cerebrospinal fluid (CSF) that can predict the development of post-hemorrhagic hydrocephalus (PHH) and shunt-dependency, as well as functional outcome in patients with subarachnoid hemorrhage (SAH). Proximity extension assay (PEA) was used to analyze CSF samples from 31 SAH patients, and 7 markers were identified as predictors of shunt dependency and 4 markers as predictors of functional outcome. These inflammatory biomarkers hold potential as predictive tools in the clinic.
Article
Cardiac & Cardiovascular Systems
Olga M. Rusiecka, Filippo Molica, Morten S. Nielsen, Axel Tollance, Sandrine Morel, Maud Frieden, Marc Chanson, Kerstin Boengler, Brenda R. Kwak
Summary: This study found that deletion of the Pannexin1 (Panx1) gene in cardiac endothelial cells can alleviate cardiac ischaemia/reperfusion (I/R) injury and improve left ventricular function recovery. This cardioprotective effect seems to be mediated through its influence on cardiac mitochondria rather than reducing the inflammatory response. Therefore, Panx1 may represent a new target for controlling cardiac reperfusion damage.
CARDIOVASCULAR RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Sara Diana Lolansen, Nina Rostgaard, Tenna Capion, Nicolas H. Norager, Markus Harboe Olsen, Marianne Juhler, Tiit Illimar Mathiesen, Nanna MacAulay
Summary: The molecular mechanisms underlying the development of posthemorrhagic hydrocephalus (PHH) remain unclear, but elevated cerebrospinal fluid (CSF) osmolality is not the cause of PHH. The pathological CSF accumulation observed in these patients is instead attributed to other pathological alterations associated with the abnormal presence of blood within the CSF compartments following subarachnoid hemorrhage (SAH).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Sara Diana Lolansen, Dagne Barbuskaite, Fenghui Ye, Jianming Xiang, Richard F. Keep, Nanna MacAulay
Summary: This study elucidated the molecular mechanisms underlying the development of hydrocephalus in spontaneously hypertensive rats (SHRs), and found that it is not associated with elevated intracranial pressure (ICP) and does not require increased cerebrospinal fluid (CSF) secretion or inefficient CSF drainage. This type of hydrocephalus is not life-threatening and occurs due to unknown disturbances in CSF dynamics.
FLUIDS AND BARRIERS OF THE CNS
(2023)
Article
Biochemistry & Molecular Biology
Trine L. Toft-Bertelsen, Soren Norge Andreassen, Nina Rostgaard, Markus Harboe Olsen, Nicolas H. Norager, Tenna Capion, Marianne Juhler, Nanna Macaulay
Summary: The lipidomic signature of CSF in patients with subarachnoid hemorrhage suggests dysregulation of lipids and potential biomarkers for future treatment options.
Review
Clinical Neurology
Shai David Ben-Shoshan, Sara Diana Lolansen, Tiit Illimar Mathiesen, Nanna Macaulay
Summary: This systematic review aims to explore the molecular mechanisms underlying posthemorrhagic hydrocephalus (PHH) by evaluating existing literature on increased CSF secretion and impaired CSF absorption. The results suggest that the pathological accumulation of cerebrospinal fluid in PHH may arise from a combination of increased secretion and impaired absorption, which may manifest at different time scales following a hemorrhagic event.
ACTA NEUROCHIRURGICA
(2023)
Article
Multidisciplinary Sciences
Beatriche Louise Edelbo, Soren Norge Andreassen, Annette Buur Steffensen, Nanna Macaulay, Christian Metallo
Summary: The cerebrospinal fluid (CSF) provides mechanical protection for the brain and serves as a brain dispersion route for nutrients, hormones, and metabolic waste. CSF secretion rate is elevated in the dark phase and shows similarities in day-active humans and nocturnal rats, suggesting circadian regulation. Transcriptomic and metabolomic analysis reveals significant fluctuation in CSF metabolites and differential expression of choroid plexus genes between light and dark phases, indicating light-dark phase-mediated changes in rat choroid plexus and its surrounding CSF. These findings provide insights into the molecular pathways governing CSF dynamics and potential applications in pathology.
Article
Cell Biology
Nanna Macaulay, Trine L. Toft-Bertelsen
Summary: The choroid plexus is a crucial tissue in the brain that secretes cerebrospinal fluid and maintains electrolyte balance. It is regulated by various membrane transporters and plays a vital role in controlling potassium levels in the brain. This dual function of the choroid plexus is important for overall brain function.
Article
Clinical Neurology
Nina Rostgaard, Markus Harboe Olsen, Sara Diana Lolansen, Nicolas Hernandez Norager, Peter Plomgaard, Nanna Macaulay, Marianne Juhler
Summary: By using a proteomic approach, this study aimed to identify potential protein biomarkers in cerebrospinal fluid (CSF) that can differentiate between obstructive and communicating hydrocephalus, as well as predict surgical outcomes. The analysis identified several proteins with differential abundance in CSF from hydrocephalus patients compared to control subjects, and identified ten proteins that can predict response to surgery in obstructive hydrocephalus.
ACTA NEUROCHIRURGICA
(2023)