Article
Neurosciences
Lunbin Deng, Michelle Dourado, Rebecca M. Reese, Kevin Huang, Shannon D. Shields, Kimberly L. Stark, James Maksymetz, Han Lin, Joshua S. Kaminker, Min Jung, Oded Foreman, Janet Tao, Hai Ngu, Victory Joseph, Meron Roose-Girma, Lucinda Tam, Susanne Lardell, Linnea Strid Orrhult, Paul Karila, Julien Allard, David H. Hackos
Summary: Loss-of-function mutations in Nav1.7 cause congenital insensitivity to pain. However, the overexpression of enkephalin, an endogenous opioid receptor agonist, does not play a role in the observed analgesia. Furthermore, Nav1.7 function is required for the initiation of C-fiber action potentials, explaining the observed insensitivity to pain.
Review
Critical Care Medicine
Simon Parlow, Melissa Fay Lepage-Ratte, Richard G. Jung, Shannon M. Fernando, Sarah Visintini, Lee H. Sterling, Pietro Di Santo, Trevor Simard, Juan J. Russo, Marino Labinaz, Benjamin Hibbert, Jerry P. Nolan, Bram Rochwerg, Rebecca Mathew
Summary: A systematic review and meta-analysis compared the use of volatile anaesthetics to conventional sedation in patients admitted with ROSC after OHCA. The results suggested that volatile anaesthetics may be associated with a decreased duration of mechanical ventilation, but the certainty of evidence was low.
Article
Biochemistry & Molecular Biology
Alican Gulsevin, Andrew M. Glazer, Tiffany Shields, Brett M. Kroncke, Dan M. Roden, Jens Meiler
Summary: This study identifies the binding site of veratridine (VTD) on the cardiac sodium ion channel (Na(V)1.5) using docking calculations and high-throughput electrophysiology experiments. The results suggest that VTD binds near the cytoplasmic mouth of the channel pore, potentially indicating an allosteric inactivation mechanism for VTD at Na(V)1.5.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Food Science & Technology
Rafael Gonzalez-Cano, M. Carmen Ruiz-Cantero, Miriam Santos-Caballero, Carlos Gomez-Navas, Miguel A. Tejada, Francisco R. Nieto
Summary: Tetrodotoxin (TTX) is a potent neurotoxin that blocks voltage-gated sodium channels, exhibiting promising analgesic effects in treating neuropathic pain. However, it can also produce major toxic effects at therapeutic doses, necessitating careful consideration for clinical use. Research indicates potential therapeutic effects of other natural toxins that selectively block TTX-sensitive VGSCs for alleviating neuropathic pain.
Article
Pharmacology & Pharmacy
Matyas C. Foldi, Krisztina Pesti, Katalin Zboray, Adam V. Toth, Tamas Hegedus, Andras Malnasi-Csizmadia, Peter Lukacs, Arpad Mike
Summary: The research found that riluzole mainly acts on Nav1.4 sodium channels by non-blocking modulation, selectively inhibiting pathological activity. Riluzole is identified as the prototype of a new class of sodium channel inhibitors, expected to selectively prevent hyperexcitability with minimal impact on normal cell activity.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Neurosciences
Sanjay S. Nair, Nikoleta Pavelkova, Claire M. Murphy, Marian Kollarik, Thomas E. Taylor-Clark
Summary: This study identified multiple Na(V)1 subtypes involved in vagal AP conduction, with Na(V)1.7 and NaV1.8 playing predominant roles and Na(V)1.6 and Na(V)1.2 contributing to a different extent based on nerve fiber type and species. Inhibition of these Na(V)1 may impact autonomic regulation of visceral organs.
JOURNAL OF NEUROPHYSIOLOGY
(2023)
Article
Anesthesiology
Iris A. Speigel, Hugh C. Hemmings
Summary: The study reveals that isoflurane inhibits synaptic vesicle exocytosis from hippocampal glutamatergic neurones and GABAergic interneurones in a cell-type-specific manner depending on their expression of voltage-gated sodium channel subtypes.
BRITISH JOURNAL OF ANAESTHESIA
(2021)
Article
Multidisciplinary Sciences
Enqiang Chang, Yangyang Wang, Ruilou Zhu, Lingzhi Wu, Yitian Yang, Shuang Zeng, Ningtao Li, Xiaoguo Ruan, Mingyang Sun, Wei Zhang, Jun Zhou, Mengrong Miao, Hui Zhi, Hailin Zhao, Qian Chen, Qizhe Sun, Emer Chang, Albert Chang, Tingting Zhang, Xinfang He, Kan Liu, Songhua Ma, Weizhong Zhu, Youming Zhang, Luca Magnani, Daqing Ma, Jiaqiang Zhang
Summary: By using single-cell RNA sequencing, whole-cell patch clamp, and calcium transient techniques, we investigated the effects of propofol and sevoflurane on the gene transcriptome and ion channels in human fetal prefrontal cortex cells. Both propofol and sevoflurane promoted microgliosis, but only sevoflurane decreased the transcriptional similarity of microglia. Both anesthetics transiently altered the transcriptome profiling of various cell types, such as microglia, excitatory neurons, interneurons, astrocytes, and oligodendrocyte progenitor cells, for less than 2 hours. Our study provides valuable insights for future mechanistic studies of general anesthetics in clinical settings.
Article
Biochemistry & Molecular Biology
Jessica S. Reimche, Robert E. del Carlo, Edmund D. Brodie, Joel W. McGlothlin, Karen Schlauch, Michael E. Pfrender, Edmund D. Brodie, Normand Leblanc, Chris R. Feldman
Summary: The repeated evolution of tetrodotoxin (TTX) resistance provides a model for studying convergent evolution mechanisms. In investigating garter snakes (Thamnophis) that prey on TTX-bearing newts (Taricha), it was found that there is extensive variation in resistance at different biological scales. However, one species of Thamnophis, Th. couchii, did not show functional variation in certain genetic loci or differences in candidate gene expression, suggesting that historical contingencies may play a role in the local adaptation of different species of Thamnophis.
Article
Veterinary Sciences
M. McMillan
Summary: The audit of carbon footprint in a single centre revealed that significant reductions in oxygen and inhaled anaesthetic agent consumption, as well as greenhouse gas emissions and financial expenditure, can be achieved by adapting practices. Different breathing systems and flow rates based on animal weight were suggested to reduce oxygen and anaesthetic agent usage, indicating a potential reduction of up to 97% in anaesthetics. By implementing these changes, the carbon footprint of inhaled anaesthetic agents could be reduced by 63%.
JOURNAL OF SMALL ANIMAL PRACTICE
(2021)
Article
Multidisciplinary Sciences
Marion Pierre, Mohammed Djemai, Hugo Poulin, Mohamed Chahine
Summary: Cardiomyocytes derived from patient-specific induced pluripotent stem cells successfully model the pathogenic mechanisms of various channelopathies, including experiments involving knockout of the cardiac sodium channel. A Na(V)1.5 KO iPSC line capable of differentiating into cardiomyocytes was developed using CRISPR/Cas9 technology. Changes in action potentials (APs) and electrophysiological properties in Na(V)1.5 KO iPSC-CMs, as well as the impact of a long QT syndrome 3 (LQT3) variant on Na+ channel function, were observed.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Estelle Moubarak, Yanis Inglebert, Fabien Tell, Jean -Marc Goaillard
Summary: The shape of action potential (AP) is crucial in regulating neurotransmitter release and distinguishing neuronal populations. While variations in AP shape between different neuronal types are mainly attributed to differences in ion channel expression, the influence of dendritic morphology on AP shape has been suggested. This study investigates the relationship between dendritic morphology and AP shape in rat SNc DA neurons. The results demonstrate that dendritic morphology plays a significant role in defining the electrophysiological properties of SNc DA neurons.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Biology
Igor Melnikov, Philipp Orekhov, Maksim Rulev, Kirill Kovalev, Roman Astashkin, Dmitriy Bratanov, Yury Ryzhykau, Taras Balandin, Sergei Bukhdruker, Ivan Okhrimenko, Valentin Borshchevskiy, Gleb Bourenkov, Christoph Mueller-Dieckmann, Peter van der Linden, Philippe Carpentier, Gordon Leonard, Valentin Gordeliy, Alexander Popov
Summary: This work examines the molecular-level interactions between small hydrophobic molecules and membrane proteins (MPs), particularly focusing on noble gases and their potential role in anesthesia.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Victor N. Ierusalimsky, Pavel M. Balaban, Evgeny S. Nikitin
Summary: Electrophysiological and genetic studies have identified two major subclasses of L5 neocortical pyramidal neurons, with one subclass expressing KCa3.1 channels and the other exhibiting weak afterhyperpolarization. This study demonstrates that Nav1.6 channels, rather than KCa3.1 channels, have an impact on the threshold, dynamics, and coding abilities of these neurons. The findings suggest a link between Nav1.6 function and the ability of L5 neurons to encode high frequencies.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Shana L. Geffeney, Jennie Ann Cordingley, Kenyon Mitchell, Charles T. Hanifin
Summary: Multiple animal species have developed resistance to the neurotoxin tetrodotoxin (TTX) by altering the amino acid substitutions in voltage-gated sodium ion channels (VGSCs). This study demonstrates that positionally convergent substitutions of amino acids do not generate similar patterns among TTX-resistant animal lineages, suggesting that flexibility and movement of the protein may play a greater role in causing changes in TTX block.