Article
Biochemistry & Molecular Biology
Xinhe Yang, Shuai Chen, Shuo Zhang, Sai Shi, Rui Zong, Yiting Gao, Bingcai Guan, Nikita Gamper, Haixia Gao
Summary: Zinc serves as a cofactor for numerous enzymes, transcription factors, receptors, and other proteins. It acts as an important signaling molecule and can activate Kv7 channels, protecting neurons from overactivity.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Neurosciences
Debora Laker, Frederik Tolle, Michael Stegen, Marco Heerdegen, Rudiger Kohling, Timo Kirschstein, Jakob Wolfart
Summary: The slow afterhyperpolarizing potential (sAHP) determines the discharge behavior of neurons, particularly in dentate granule cells (DGCs) where burst-like firing is the default phenotype. sAHP is mediated by K(v)7 and K(ir)6 channels, and its inhibition affects burst firing and synaptic plasticity.
Article
Multidisciplinary Sciences
Mickael Zbili, Sylvain Rama, Maria-Jose Benitez, Laure Fronzaroli-Molinieres, Andrzej Bialowas, Norah Boumedine-Guignon, Juan Jose Garrido, Dominique Debanne
Summary: Blocking excitatory synaptic receptors leads to an increase in synaptic transmission and intrinsic excitability in the CA3 region, with intrinsic plasticity mediated by a reduction in Kv1.1 channel density. Activity-deprived neurons show down-regulation of axonal Kv1.1 channels, resulting in functional synergy between synaptic strength and intrinsic excitability.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Pharmacology & Pharmacy
Moawiah M. Naffaa, Ola A. Al-Ewaidat
Summary: KCNQ-encoded potassium channels play diverse roles in human tissues, affecting various physiological processes and pathophysiological conditions. New, more selective and potent molecules targeting Kv7 channels are desired for effective therapies. Understanding the structure and function of human KCNQ-encoded channels helps in achieving these therapeutic goals.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Andrology
Joongwon Choi, Deok H. Han, Mee R. Chae, Hyun H. Sung, Su J. Kang, Jimin Shin, Sung W. Lee
Summary: The study investigated the molecular characteristics and physiological roles of Kv7 channels in human prostatic smooth muscle (HPrSM). KCNQ4, KCNQ5, and KCNE4 isoforms were predominantly expressed in HPrSM cells, while KCNQ1, KCNQ5, and KCNE3 isoforms were most abundantly expressed in human prostatic tissues. ML213 induced concentration-dependent relaxation of HPrSM strips by activating Kv7.2/7.4/7.5 channels, and this effect was attenuated by pretreatment with the Kv7.1-7.5 blocker XE991.
Article
Neurosciences
Salvatore Incontro, Malika Sammari, Fodil Azzaz, Yanis Inglebert, Norbert Ankri, Michael Russier, Jacques Fantini, Dominique Debanne
Summary: Research shows that Kv7 channel activity is upregulated in O-LM interneurons following induction of presynaptic long-term synaptic depression, leading to a synergistic long-term depression of intrinsic excitability. This process involves endocannabinoid biosynthesis and a persistent interaction with Kv7 channels.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Amanda Henton, Yanjun Zhao, Thanos Tzounopoulos
Summary: Damage to sensory organs triggers compensatory plasticity mechanisms in sensory cortices, resulting in restored cortical responses and recovery of perceptual detection thresholds. In this study, the authors investigated the changes in intrinsic properties and biophysical mechanisms following noise-induced peripheral damage. They found a specific reduction in the intrinsic excitability of parvalbumin-expressing neurons in the auditory cortex, associated with an increase in KCNQ potassium channel activity. These findings provide insights into the cell type and channel-specific plasticity mechanisms involved in hearing loss and related disorders.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Medicine, Research & Experimental
Marta Villegas-Esguevillas, Suhan Cho, Alba Vera-Zambrano, Jae Won Kwon, Bianca Barreira, Gocken Telli, Jorge Navarro-Dorado, Daniel Morales-Cano, Beatriz de Olaiz, Laura Moreno, Iain Greenwood, Francisco Perez-Vizcaino, Sung Joon Kim, Belen Climent, Angel Cogolludo
Summary: In this study, the effects of the novel KV7 channel agonist URO-K10 on the pulmonary vasculature were investigated. URO-K10 was found to be a more effective relaxant of pulmonary arteries compared to classical KV7 activators. It also exhibited antiproliferative effects in human pulmonary artery smooth muscle cells. These findings suggest that URO-K10 could be a promising drug for the treatment of pulmonary arterial hypertension.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
DanDan Geng, Yaning Li, Rong Zheng, Runmeng Wang, Bo Yang, Huaxing Zhang, Yang Zhang, Fan Zhang
Summary: This study investigated the effects of pentacyclic triterpenes on Kv7 channels and found that echinocystic acid was the most potent inhibitor, which could be used to further understand the pharmacological functions of neuronal Kv7 channels.
MOLECULAR PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Leandro M. Alonso, Mara C. P. Rue, Eve Marder
Summary: Neurons use intracellular calcium concentrations to regulate their excitability, and models with multiple sensors can distinguish different activity patterns. However, previous models with multiple sensors displayed instabilities leading to unbounded growth of conductances. By introducing a nonlinear degradation term, we prevent conductances from growing beyond a certain bound. The modified model can recover from perturbations and shows that caution must be exercised in interpreting manipulations that mimic increased neuronal activity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Nicholas C. Vierra, Samantha C. O'Dwyer, Collin Matsumoto, L. Fernando Santana, James S. Trimmer
Summary: In mammalian brain neurons, membrane depolarization triggers Ca2+ influx through voltage-gated Ca2+ channels, leading to diverse cellular responses, including gene expression. The L-type Ca2+ channels in neuronal soma and dendrites play a key role in this process. The organization of signaling complexes by Kv2.1 at endoplasmic reticulum-plasma membrane junctions enhances the clustering and activity of Cav1.2 channels, impacting somatic Ca2+ signals and excitation-transcription coupling.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
Som P. Singh, Matthew William, Mira Malavia, Xiang-Ping Chu
Summary: The broad distribution of voltage-gated potassium channels in the human body makes them critical for studying physiological and pathological functions. In neural tissue, KCNQ channels play a significant role in maintaining homeostasis and regulating neural plasticity. Recent research has also highlighted their importance in pharmacotherapeutic and pathological roles, particularly in motor disorders. Understanding the behavior of these channels can provide insights for clinical approaches to chronic pain and guide pharmacotherapeutic developments.
Article
Neurosciences
F. Locatelli, T. Soda, I Montagna, S. Tritto, L. Botta, F. Prestori, E. D'Angelo
Summary: Research has found that excitatory synapses on Golgi cells in the cerebellum exhibit a unique voltage dependence in long-term plasticity, with activation of T-type and L-type Ca2+ channels playing important roles in inducing LTP and LTD. Additionally, there is an inverted relationship between plasticity at mossy fiber-Golgi cell synapses and mossy fiber-granule cell synapses in terms of voltage dependence.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Clinical Neurology
Arzu Citak, Erkan Kilinc, Ibrahim Ethem Torun, Seyit Ankarali, Yasar Dagistan, Hamit Yoldas
Summary: This study investigated the effects of certain transient receptor potential channels and voltage-gated potassium channels on the release of calcitonin gene-related peptide. The results showed that agonists of these channels induced the release of calcitonin gene-related peptide, which could be blocked or reduced by specific antagonists and retigabine. This suggests that antagonists of these channels or retigabine may be effective in migraine therapy by inhibiting the neurogenic inflammation that requires calcitonin gene-related peptide release.
Article
Biology
Shashank Pant, Jiaren Zhang, Eung Chang Kim, Kin Lam, Hee Jung Chung, Emad Tajkhorshid
Summary: Research using molecular dynamics simulations and electrophysiology has revealed the allosteric role of phosphatidylinositol-4,5-bisphosphate (PIP2) in the activation of K(v)7.2 channels, influencing protein conformation and correlated motions.
COMMUNICATIONS BIOLOGY
(2021)
Article
Neurosciences
Karina P. Abrahao, Jessica H. Chancey, C. Savio Chan, David M. Lovinger
NEUROPSYCHOPHARMACOLOGY
(2017)
Article
Anatomy & Morphology
Albert J. Hunt, Rajan Dasgupta, Shivakumar Rajamanickam, Zhiying Jiang, Michael Beierlein, C. Savio Chan, Nicholas J. Justice
BRAIN STRUCTURE & FUNCTION
(2018)
Article
Neurosciences
Francois David, Nihan Carcak, Szabina Furdan, Filiz Onat, Timothy Gould, Adam Meszaros, Giuseppe Di Giovanni, Vivian M. Hernandez, C. Savio Chan, Magor L. Lorincz, Vincenzo Crunelli
JOURNAL OF NEUROSCIENCE
(2018)
Article
Neurosciences
Jean-Francois Poulin, Giuliana Caronia, Caitlyn Hofer, Qiaoling Cui, Brandon Helm, Charu Ramakrishnan, C. Savio Chan, Daniel A. Dombeck, Karl Deisseroth, Rajeshwar Awatramani
NATURE NEUROSCIENCE
(2018)
Article
Biology
Luis Carrillo-Reid, Michelle Day, Zhong Xie, Alexandria E. Melendez, Jyothisri Kondapalli, Joshua L. Plotkin, David L. Wokosin, Yu Chen, Geraldine J. Kress, Michael Kaplitt, Ema Ilijic, Jaime N. Guzman, S. Savio Chan, D. James Surmeier
Article
Neurosciences
Zachary A. Abecassis, Brianna L. Berceau, Phyo H. Win, Daniela Garcia, Harry S. Xenias, Qiaoling Cui, Arin Pamukcu, Suraj Cherian, Vivian M. Hernandez, Uree Chon, Byung Kook Lim, Yongsoo Kim, Nicholas J. Justice, Raj Awatramani, Bryan M. Hooks, Charles R. Gerfen, Simina M. Boca, C. Savio Chan
JOURNAL OF NEUROSCIENCE
(2020)
Article
Cell Biology
Elahe Ganji, C. Savio Chan, Christopher W. Ward, Megan L. Killian
Summary: This study aimed to evaluate the feasibility of non-invasive optogenetic stimulation of skeletal muscle in mice. By inducing specific gene expression in skeletal muscle and using transdermal blue light exposure for muscle contraction experiments, the study demonstrated the impact of optogenetic stimulation on sustained muscle contraction.
CONNECTIVE TISSUE RESEARCH
(2021)
Article
Cell Biology
Jean-Francois Poulin, Milagros Pereira Luppi, Caitlyn Hofer, Giuliana Caronia, Pei-Ken Hsu, C. Savio Chan, Rajeshwar Awatramani
DEVELOPMENTAL CELL
(2020)
Article
Neurosciences
Arin Pamukcu, Qiaoling Cui, Harry S. Xenias, Brianna L. Berceau, Elizabeth C. Augustine, Isabel Fan, Saivasudha Chalasani, Adam W. Hantman, Talia N. Lerner, Simina M. Boca, C. Savio Chan
JOURNAL OF NEUROSCIENCE
(2020)
Article
Neurosciences
Matthew H. Higgs, James A. Jones, C. Savio Chan, Charles J. Wilson
Summary: Neurons in the external globus pallidus (GPe) are autonomous pacemakers and receive periodic spontaneous inhibitory synaptic currents (IPSCs) from both parvalbumin (PV) and Npas1-expressing neurons. Optogenetic stimulation confirmed that the input arose from local neurons subject to striatal inhibition. PV neurons provided most of the active unitary inputs to both cell types, while the local network contributes to irregular firing in both PV and Npas1 neurons.
JOURNAL OF NEUROPHYSIOLOGY
(2021)
Article
Neurosciences
Qiaoling Cui, Xixun Du, Isaac Y. M. Chang, Arin Pamukcu, Varoth Lilascharoen, Brianna L. Berceau, Daniela Garcia, Darius Hong, Uree Chon, Ahana Narayanan, Yongsoo Kim, Byung Kook Lim, C. Savio Chan
Summary: The study reveals that direct-pathway striatal projection neurons not only innervate the external globus pallidus (GPe), but also selectively target Npas1(+) neurons within it. In a Parkinson's disease model, this projection is significantly strengthened, leading to movement suppression. This highlights the critical role of the direct-pathway striatal input to GPe as a circuit mechanism for regulating movement in both healthy and parkinsonian states.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Qiaoling Cui, Arin Pamukcu, Suraj Cherian, Isaac Y. M. Chang, Brianna L. Berceau, Harry S. Xenias, Matthew H. Higgs, Shivakumar Rajamanickam, Yi Chen, Xixun Du, Yu Zhang, Hayley McMorrow, Zachary A. Abecassis, Simina M. Boca, Nicholas J. Justice, Charles J. Wilson, C. Savio Chan
Summary: By using novel driver lines, this study provides an exhaustive investigation of electrophysiological studies of GPe neuron subtypes, revealing that Npr3(+) neurons and Kcng4(+) neurons are distinct subclasses of Npas1(+) and PV+ neurons, respectively. Through optogenetics and machine learning-based tracking, unique behavioral structures generated by optogenetic perturbation of GPe neuron subtypes were observed, highlighting the dissociable roles of GPe neurons in regulating movement and anxiety-like behavior.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Gessynger Morais-Silva, Rianne R. Campbell, Hyungwoo Nam, Mahashweta Basu, Marco Pagliusi, Megan E. Fox, C. Savio Chan, Sergio D. Iniguez, Seth Ament, Nathan Cramer, Marcelo Tadeu Marin, Mary Kay Lobo
Summary: The altered activity of the ventral pallidum (VP) is responsible for disrupted motivation in stress and drug exposure. To investigate the role of Neuronal PAS 1-positive (Npas1+) VP neurons, we analyzed their projection targets and conducted RNA sequencing on VP Npas1+ neurons to understand their molecular identities. Chemogenetic activation of VP Npas1+ neurons modulated susceptibility to social stressors and anxiety-like behavior. Our findings reveal the circuitry, molecular identity, and stress response role of VP Npas1+ neurons.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Biology
Harry S. Xenias, Chuyu Chen, Shuo Kang, Suraj Cherian, Xiaolei Situ, Bharanidharan Shanmugasundaram, Guoxiang Liu, Giuseppe Scesa, C. Savio Chan, Loukia Parisiadou
Summary: Studies of mouse models with different mutations of the LRRK2 gene associated with Parkinson's disease reveal distinct alterations at multiple levels, including electrochemical, electrophysiological, molecular, and behavioral. The findings suggest that LRRK2 mutations affect striatal function, but the specific changes vary between different mutations. The results provide mechanistic insights for developing treatment strategies for Parkinson's disease patients.
COMMUNICATIONS BIOLOGY
(2022)
Editorial Material
Neurosciences
Connor D. Courtney, C. Savio Chan
Summary: Two recent studies provide in vivo evidence that the external globus pallidus (GPe) not only regulates motor control but also encodes non-motor information through cell-type division of labor, processing sensory stimulation and reward cues.
TRENDS IN NEUROSCIENCES
(2023)