Article
Chemistry, Multidisciplinary
Yangmei Li, Chao Chang, Zhi Zhu, Lan Sun, Chunhai Fan
Summary: The dysfunction of voltage-gated calcium channels leading to a deficiency in Ca2+ fluxes is associated with calcium channelopathies such as epilepsy and periodic paralysis. By using resonant terahertz waves, researchers have demonstrated enhanced selectivity and conductance of Ca2+, potentially offering therapeutic interventions in correcting calcium channel deficiencies and inducing apoptosis in tumor cells.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Pharmacology & Pharmacy
Paz Duran, Santiago Loya-Lopez, Dongzhi Ran, Cheng Tang, Aida Calderon-Rivera, Kimberly Gomez, Harrison J. Stratton, Sun Huang, Ya-ming Xu, E. M. Kithsiri Wijeratne, Samantha Perez-Miller, Zhiming Shan, Song Cai, Anna T. Gabrielsen, Angie Dorame, Kyleigh A. Masterson, Omar Alsbiei, Cynthia L. Madura, Guoqin Luo, Aubin Moutal, John Streicher, Gerald W. Zamponi, A. A. Leslie Gunatilaka, Rajesh Khanna
Summary: This study identified argentatin C, a compound derived from the Native American medicinal plant Parthenium incanum, which can block the activity of voltage-gated sodium and calcium channels and has potential as a novel treatment for painful conditions. Experimental results demonstrated that argentatin C decreased ion currents and excitability in sensory neurons and relieved postsurgical pain in a mouse model. Therefore, argentatin C may serve as an alternative therapy for chronic pain management.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Cell Biology
Yashashwini Dinesh Subbamanda, Anamika Bhargava
Summary: This article discusses the interaction and regulation between voltage-gated calcium channels (VGCCs) and estrogen receptors. Most of the research focuses on neuronal and cardiovascular tissues, describing the modulation of VGCCs by estrogen. More physiological experiments are needed to study the regulation of VGCCs by estrogen, as well as identifying other receptors and partners involved in estrogen receptor-independent effects.
Article
Chemistry, Physical
Mehdi Yoosefian, Batool Tajaddini, Saeid Ahmadzadeh, Maryam Zeraati-Moghani, Zahra Pakdin-Parizi
Summary: Drinking excessive alcohol can cause chronic diseases and serious problems such as heart disease, high blood pressure, stroke, digestive problems, and liver disease. A molecular dynamics simulation study found that ethanol blocks calcium channels and interferes with calcium ion passage. Furthermore, calcium ions have a greater tendency to interact with residues inside the protein channel in the presence of ethanol.
JOURNAL OF MOLECULAR LIQUIDS
(2023)
Editorial Material
Multidisciplinary Sciences
Declan Manning, L. Fernando Santana
Summary: The authors of this study present an approach using functionalized nanobodies to reduce the activity of voltage-gated Ca2+ channels associated with beta(1) subunits and facilitate their removal from the surface membrane of neurons and muscle.
NATURE COMMUNICATIONS
(2022)
Article
Neurosciences
Daniel M. DuBreuil, Eduardo Javier Lopez Soto, Simon Daste, Remy Meir, Daniel Li, Brian Wainger, Alexander Fleischmann, Diane Lipscombe
Summary: Functional Ca(V)2.2 channels in peripheral axons innervating skin are required for capsaicin-induced heat hypersensitivity, which may be an important therapeutic target for certain forms of chronic pain.
JOURNAL OF NEUROSCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Robert J. Lauerer, Holger Lerche
Summary: This review summarizes the importance of VGCC in the central nervous system and its association with epilepsy-related genes, providing guidance for disease-specific therapies when applicable.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Reproductive Biology
Daniel Bahena-Alvarez, Diana Millan-Aldaco, Ruth Rincon-Heredia, Nancy Escamilla-Avila, Arturo Hernandez-Cruz
Summary: In this study, the expression of high-voltage activated Ca2+ channel alpha subunits and InsP(3) and ryanodine receptors in the postnatal ovary from 3 to 16 days was analyzed using immunofluorescence and confocal microscopy. The results indicated a developmental switch of Ca2+ channel expression from oocytes to perifollicular cells during folliculogenesis, reflecting the changing roles of different cell types in response to gonadotropins.
JOURNAL OF OVARIAN RESEARCH
(2022)
Review
Neurosciences
Byoung Ju Lee, Che Ho Yang, Seung Yeon Lee, Suk-Ho Lee, Yujin Kim, Won-Kyung Ho
Summary: The coupling distance between VGCCs and synaptic vesicles determines the VGCC dependence of spontaneous release at synapses, with tightly coupled synapses showing significant VGCC contribution while loosely coupled synapses have minimal VGCC involvement.
PROGRESS IN NEUROBIOLOGY
(2022)
Article
Chemistry, Medicinal
Eleni Kaisis, Laura J. J. Thei, Gary J. J. Stephens, Mark L. L. Dallas
Summary: Cav2.2 channels are modulated by Ab(1-42) peptides, and this modulation has different effects at different concentrations. This study reveals a potential mechanistic link between amyloid accumulation and Cav2.2 channel modulation.
Review
Physiology
Rabab Rashwan, David M. Hunt, Livia S. Carvalho
Summary: Photoreceptors exhibit remarkable adaptability by adjusting gain to respond to different levels of ambient light intensity. The dynamic operating range of photoreceptors is maintained by a balance of inward and outward currents modulated by various ion channels. Potassium and calcium voltage-gated channels play crucial roles in setting the dark resting potential and synaptic signal processing, contributing significantly to visual processing.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Shuai Gao, Nieng Yan
Summary: This study reports the structures of Ca(v)1.1 bound with different drugs, revealing the molecular basis for their effects. The structures show that amlodipine and nifedipine have different impacts on Ca(v)1.1, while the two enantiomers of Bay K8644 as agonists are insufficient to maintain the activated state of the channel.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Pharmacology & Pharmacy
Tamara Timic Stamenic, Francesca M. Manzella, Stefan Maksimovic, Kathiresan Krishnan, Douglas F. Covey, Vesna Jevtovic-Todorovic, Slobodan M. Todorovic
Summary: This study further investigated the molecular mechanisms of neurosteroid-induced hypnosis. The results demonstrated the importance of the Ca(V)2.3 subtype of voltage-gated calcium channels in thalamocortical excitability and the oscillations that underlie neurosteroid-induced hypnosis.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Cell Biology
Petronel Tuluc, Tamara Theiner, Noelia Jacobo-Piqueras, Stefanie M. Geisler
Summary: Pancreatic islets secrete hormones critical for glucose homeostasis, with insulin from beta-cells being the main hormone for lowering blood glucose levels. Glucagon and somatostatin also play important roles in regulating hormone secretion. High voltage-gated Ca2+ channels are central in the release of pancreatic hormones and play a key role in diabetes.
Article
Biochemistry & Molecular Biology
Marta Martini, Giorgio Rispoli
Summary: Some sensory disorders in hearing, vestibular, and vision can be attributed to voltage-gated Ca2+ channels in sensory cells. In this study, the Na+ current flowing through L- and R-type Ca2+ channels in labyrinth hair cells was investigated. The activation and deactivation of the Na+ current in L-type channels were affected by low Ca2+ concentration, resulting in increased current amplitude. The R-type Na+ current was partially blocked by nifedipine and its current amplitude increased in low Ca2+ condition. Furthermore, the selectivity filter of R channels was less affected by external Ca2+ compared to L channels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Psychiatry
Hiroko Kotajima-Murakami, Hideo Hagihara, Atsushi Sato, Yoko Hagino, Miho Tanaka, Yoshihisa Katoh, Yasumasa Nishito, Yukio Takamatsu, Shigeo Uchino, Tsuyoshi Miyakawa, Kazutaka Ikeda
Summary: This study found that exposure to the GABA(A) receptor antagonist picrotoxin during the embryonic period induced ASD-like behavior in mice. The offspring exhibited a reduction in active interaction time in social interaction tests, and gene expression analysis showed an increase in odorant receptor gene expression. The findings suggest that impaired odorant function may contribute to social deficits in individuals with ASD.
FRONTIERS IN PSYCHIATRY
(2022)
Article
Biochemistry & Molecular Biology
Takafumi Kawai, Hirotaka Narita, Kohtarou Konno, Sharmin Akter, Rizki Tsari Andriani, Hirohide Iwasaki, Shoji Nishikawa, Norihiko Yokoi, Yuko Fukata, Masaki Fukata, Pattama Wiriyasermkul, Pornparn Kongpracha, Shushi Nagamori, Keizo Takao, Tsuyoshi Miyakawa, Manabu Abe, Kenji Sakimura, Masahiko Watanabe, Atsushi Nakagawa, Yasushi Okamura
Summary: Voltage-sensing protein TMEM266 has a unique voltage-sensing mechanism and interacts with specific splice variants. The coiled-coil region plays a significant role in forming homodimers, and the cytosolic region at the C-terminal of TMEM266 may bind to various targets. TMEM266 deficiency is associated with behavioral abnormalities.
BIOCHEMICAL JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Akito Nakao, Katsumi Hayashida, Hiroo Ogura, Yasuo Mori, Keiji Imoto
Summary: CACNA1A-related epilepsy and ataxia often come with cognitive impairments. This study found that the CACNA1A mutation leads to hippocampus-related memory and synaptic plasticity disorders.
Article
Multidisciplinary Sciences
Tomoyuki Murano, Ryuichi Nakajima, Akito Nakao, Nao Hirata, Satoko Amemori, Akira Murakami, Yukiyasu Kamitani, Jun Yamamoto, Tsuyoshi Miyakawa
Summary: The dentate gyrus (DG) plays a critical role in cognitive functions, but its information representation mechanism is not fully understood. In this study, neuronal activity in the DG of freely moving mice was recorded using Ca2+ imaging and analyzed using machine learning. The results showed that multiple types of information can be independently decoded from the activity patterns of DG neurons, and different types of information are encoded by different populations of neurons.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Editorial Material
Cell Biology
Yasuo Mori, Mizuki Omori, Akito Nakao
Summary: TRPV6 plays a pathogenic role in alcohol-associated endotoxemia, compromising intestinal barrier function. Alcohol impairs TRPV6-mediated Ca2+ absorption.
Article
Chemistry, Multidisciplinary
Naoya Ieda, Masato Sawada, Runa Oguchi, Masato Itoh, Seina Hirakata, Daisuke Saitoh, Akito Nakao, Mitsuyasu Kawaguchi, Kazunobu Sawamoto, Toshitada Yoshihara, Yasuo Mori, Hidehiko Nakagawa
Summary: We have developed an optochemical O-2 scavenging system that can control hypoxia levels in living cells by adjusting light intensity. This system utilizes rhodamine with a selenium or tellurium atom as an oxygen scavenger, which reacts with glutathione upon visible light irradiation to rapidly consume O-2. The system has a quick response time and the consumed glutathione quantum yields were calculated as approximately 5%. Using hypoxia-responsive fluorescence probe and phosphorescence lifetime imaging, we demonstrated the spatiotemporal control of O-2 consumption and its potential application in regulating calcium ion influx in hypoxic conditions.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Developmental Biology
Takayuki Mitsuhashi, Satoko Hattori, Kimino Fujimura, Shinsuke Shibata, Tsuyoshi Miyakawa, Takao Takahashi
Summary: Valproic acid (VPA) is an antiepileptic drug that inhibits epileptic activity of neurons mainly through sodium channel inhibition and GABA transaminase inhibition. It also inhibits histone deacetylases, leading to epigenetic modifications of stem/progenitor cell characteristics and affecting fetal development. Clinical studies have shown that VPA exposure in utero increases the risk of autistic features and intellectual disabilities in children. A study on mice revealed that in utero VPA exposure led to abnormal social interaction, cognitive changes, hypersensitivity to pain/heat, and impaired locomotor activity, resembling symptoms of autism spectrum disorder in humans.
DEVELOPMENTAL NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Shohei Iida, Hirotaka Shoji, Fumihiro Kawakita, Takehisa Nakanishi, Yoshiaki Matsushima, Makoto Kondo, Koji Habe, Hidenori Suzuki, Tsuyoshi Miyakawa, Keiichi Yamanaka
Summary: Intense itching reduces the quality of life and is associated with psychiatric conditions. This study used a dermatitis mouse model to evaluate psychiatric symptoms and found that Lcn2 is closely associated with anxiety symptoms, but anxiety and depression caused by chronic skin inflammation may be irreversible. Active control of skin inflammation is essential for preventing anxiety.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Hirotaka Shoji, Kazutaka Ikeda, Tsuyoshi Miyakawa
Summary: This study investigated the effects of 5-HTT deficiency on behavior, gut microbiota, and brain c-Fos expression. The findings revealed abnormal behaviors including decreased locomotor activity, reduced pain sensitivity, increased anxiety and depression-related behavior, and altered gut microbiota composition in 5-HTT-/- mice. The expression of c-Fos in certain brain regions was also different from normal. These results indicate that 5-HTT-/- mice serve as a valid animal model to study anxiety and depression.
Article
Neurosciences
Mohamed Darwish, Satoko Hattori, Hirofumi Nishizono, Tsuyoshi Miyakawa, Nozomu Yachie, Keizo Takao
Summary: GlyR alpha 4 subunit is mainly expressed in the hindbrain and midbrain of mice, and has lower expression in other regions of the brain. The expression of GlyR alpha 4 increases during brain development. Mutant mice with Glra4 deficiency show changes in startle response, social behavior, and anxiety-like behavior.
Article
Psychiatry
Hideo Hagihara, Tomoyuki Murano, Tsuyoshi Miyakawa
Summary: The study suggests that changes in brain pH, expressed as pH, are associated with various neuropsychiatric disorders. The expression patterns of pH-associated genes in these disorders were analyzed in human patients and mouse models, showing abnormal expression levels. Furthermore, astrocytes were identified as the cell type with the highest acidity-related gene expression. These findings indicate that the expression pattern of pH-associated genes may serve as a surrogate for pH changes in brain cells and provide insights into the pathophysiology of neuropsychiatric disorders.
FRONTIERS IN PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Yashuang Ping, Kenji Ohata, Kenji Kikushima, Takumi Sakamoto, Ariful Islam, Lili Xu, Hengsen Zhang, Bin Chen, Jing Yan, Fumihiro Eto, Chiho Nakane, Keizo Takao, Tsuyoshi Miyakawa, Katsuya Kabashima, Miho Watanabe, Tomoaki Kahyo, Ikuko Yao, Atsuo Fukuda, Koji Ikegami, Yoshiyuki Konishi, Mitsutoshi Setou
Summary: As an important neurotransmitter, glutamate functions in the majority of excitatory synapses in the human brain. The metabolic pathway of glutamate is complex, and the exact role of glutamate pool in neurons remains unclear. This study utilized Ttll1 and Ttll7 knockout mice to investigate the impact of tubulin polyglutamylation on neuronal behavior. Matrix-assisted laser desorption/ionization (MALDI) Imaging mass spectrometry (IMS) analysis revealed increased levels of glutamate in the brains of knockout mice, suggesting that tubulin polyglutamylation by TTLLs acts as a reservoir of glutamate in neurons and modulates other glutamate-related amino acids.
Article
Neurosciences
Hirotaka Shoji, Hiroshi Kunugi, Tsuyoshi Miyakawa
Summary: This study investigated the acute and chronic effects of oral administration of capric acid (C10) on behavior in mice. The results showed that high doses of C10 decreased body weight, distance traveled, and increased anxiety-like behavior, while low doses of C10 increased distance traveled. Repeated administration of C10 at a high dose for more than 21 days led to lower body weight and decreased depression-related behavior.
NEUROPSYCHOPHARMACOLOGY REPORTS
(2022)
Meeting Abstract
Ophthalmology
Chieko Koike, Tesshu Hori, Keishun Iwao, Shohei Ikuta, Satoko Hattori, Keizo Takao, Tsuyoshi Miyakawa
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Clinical Neurology
Masayoshi Nagai, Kenji Iemura, Takako Kikkawa, Sharmin Naher, Satoko Hattori, Hideo Hagihara, Koh-ichi Nagata, Hayato Anzawa, Risa Kugisaki, Hideki Wanibuchi, Takaya Abe, Kenichi Inoue, Kengo Kinoshita, Tsuyoshi Miyakawa, Noriko Osumi, Kozo Tanaka
Summary: The deficiency of CHAMP1 gene causes intellectual disability and is associated with delayed neuronal development and behavioral defects observed in mice models.
BRAIN COMMUNICATIONS
(2022)