Article
Pharmacology & Pharmacy
Frank S. Choveau, Ismail Ben Soussia, Delphine Bichet, Chatelain C. Franck, Sylvain Feliciangeli, Florian Lesage
Summary: This study investigates how the inhibitory potassium channels of the TREK1/TRAAK family are affected by multiple stimuli like temperature, membrane stretch, polyunsaturated fatty acids, and pH. Through pharmacological experiments, it was found that the cytoplasmic domain pCt, arachidonic acid, and extracellular pH converge to the same gate within the channel. Additionally, the study provides evidence that the up and down conformations identified by crystallography do not correspond to the open and closed states of these channels.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Linus J. Conrad, Peter Proks, Stephen J. Tucker
Summary: This passage discusses a voltage-dependent gating process in the TREK-2 K+ channel, which can be modulated by small molecule agonists and high internal K+ concentrations. It is found that high ionic-strength can inhibit the channel conductance, while the activatory effect of BL1249 on channel open probability persists under these conditions. The influence of negatively charged activators like BL1249 on permeation is consistent with an electrostatic mechanism, suggesting complexity in their effect on channel gating.
Article
Neurosciences
Victoria Garcia-Morales, Angela Gento-Caro, Federico Portillo, Fernando Montero, David Gonzalez-Forero, Bernardo Moreno-Lopez
Summary: In this study, it was found that ROCK2 mediates adjustment of motoneuron intrinsic membrane excitability by modulating TASK1 channels, and various neurotransmitters and neuromodulators can impact neuronal excitability through this pathway. Additionally, this regulation involves G-protein-coupled receptors, downstream ROCK2 activation, and subsequent inhibition of TASK1 channels.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Endocrinology & Metabolism
Yinlam Li, Li Jin, Yanquan Li, Jianing Qian, Zhengquan Wang, Xiaoguo Zheng, Chong Xie, Xuelian Zhang, Hefeng Huang, Yuchuan Zhou
Summary: This study reveals the involvement of LPA in regulating human sperm motility by enhancing glycolysis and activating L-type calcium channels. The findings shed new light on the understanding of the causes of asthenozoospermia and suggest that LPA could be used as a novel therapeutic agent to improve sperm function and fertilizing capacity.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Chemistry, Medicinal
Shanthi Nagarajan, Zu Yuan Qian, Parthiban Marimuthu, Nabil J. Alkayed, Sanjiv Kaul, Anthony P. Barnes
Summary: Through a combined computational and experimental approach, critical residues and properties within the lipid-binding pocket responsible for detecting 14,15-EET and other eicosanoids were identified. The study suggests that hydrophobic and positively charged residues in the receptor-binding pocket are prerequisites for recognizing lipid ligands, aiding in understanding the binding mechanism of GPCRs to 14,15-EET.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Chemistry, Medicinal
Dongchen An, Ernesto Lopes Pinheiro-Junior, Laszlo Beress, Irina Gladkikh, Elena Leychenko, Eivind A. B. Undheim, Steve Peigneur, Jan Tytgat
Summary: AsKC11, a Kunitz peptide found in the venom of A. sulcata, is the first peptide shown to directly activate neuronal GIRK1/2 channels independent from Gi/o protein activity, without affecting the inward-rectifier potassium channel (IRK1) and with only a minor effect on K(V)1.6 channels. Thus, AsKC11 is a novel activator of GIRK channels resulting in larger K+ currents because of an increased chord conductance.
Article
Multidisciplinary Sciences
Bettina Kolen, Bart Borghans, Daniel Kortzak, Victor Lugo, Cora Hannack, Raul E. Guzman, Ghanim Ullah, Christoph Fahlke
Summary: In glutamatergic neurons, vesicular glutamate transporters act as H+/anion exchangers for selective glutamate accumulation in synaptic vesicles. This study reveals that VGLUT1 functions as H+-glutamate exchanger with variable transport coupling and as a Cl- efflux pathway through an aqueous anion channel. Mathematical modeling demonstrates that H+ coupling enables selective glutamate accumulation, while VGLUT1's Cl- channel function increases transport efficiency.
NATURE COMMUNICATIONS
(2023)
Article
Pharmacology & Pharmacy
Viktor Burstrom, Richard agren, Nibal Betari, Marta Valle-Leon, Emilio Garro-Martinez, Francisco Ciruela, Kristoffer Sahlholm
Summary: In this study, a novel nanoluciferase complementation assay was used to investigate the dopamine-induced recruitment of beta-arrestin2 (beta arr2) and G protein-coupled receptor kinase-2 (GRK2) to the D4 receptor. The desensitization of D4 receptor-evoked G protein-coupled inward rectifier potassium (GIRK) current responses was also studied. The results showed that coexpression of GRK2 enhanced the potency of dopamine to induce beta arr2 recruitment to the D4 receptor and accelerated the rate of desensitization of D4 receptor-evoked GIRK responses.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Tamer M. Gamal El-Din, Timothy Lantin, Christopher W. Tschumi, Barbara Juarez, Meagan Quinlan, Julia H. Hayano, Jin Li, Larry S. Zweifel, William A. Catterall
Summary: Autism spectrum disorder affects over 1% of children in the United States, resulting in social interaction deficits, repetitive behaviors, and communication disorders. Genetic analysis through genome sequencing has identified over 500 genes with mutations in ASD, suggesting that altered control of action potential generation by gating pore current through mutant K(v)7 channels may be a potential pathogenic mechanism in autism.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Gastroenterology & Hepatology
Steffen Pfeuffer, Thomas Muentefering, Leoni Rolfes, Frederike Anne Straeten, Susann Eichler, Joel Gruchot, Vera Dobelmann, Tim Prozorovski, Boris Goerg, Mihael Vucur, Carsten Berndt, Patrick Kury, Tobias Ruck, Stefan Bittner, Dominik Bettenworth, Thomas Budde, Tom Luedde, Sven G. Meuth
Summary: KCNK9 regulates inflammatory bowel disease by modulating intracellular calcium concentration and supporting epithelial cell survival. Its deficiency or pharmacologic blockade worsens colitis, while increased expression of KCNK3 is associated with beneficial outcomes but does not prevent apoptosis.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Chemistry, Medicinal
Ilyas Berhane, Niyada Hin, Ajit G. Thomas, Qian Huang, Chi Zhang, Vijayabhaskar Veeravalli, Ying Wu, Justin Ng, Jesse Alt, Camilo Rojas, Hiroe Hihara, Mika Aoki, Kyoko Yoshizawa, Tomoki Nishioka, Shuichi Suzuki, Shao-Qiu He, Qi Peng, Yun Guan, Xinzhong Dong, Srinivasa N. Raja, Barbara S. Slusher, Rana Rais, Takashi Tsukamoto
Summary: A orally available positive allosteric modulator of MRGPRX1 has been discovered, which shows potential in treating neuropathic pain.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Ryuta Sugihara, Manabu Taneike, Tomokazu Murakawa, Takahito Tamai, Hiromichi Ueda, Rika Kitazume-Taneike, Takafumi Oka, Yasuhiro Akazawa, Hiroki Nishida, Kentaro Mine, Ayana Hioki, Jumpei Omi, Shigemiki Omiya, Junken Aoki, Kazutaka Ikeda, Kazuhiko Nishida, Makoto Arita, Osamu Yamaguchi, Yasushi Sakata, Kinya Otsu
Summary: Heart failure is a major cause of death in developed countries, and cell death is involved in its development. iPLA(2)& beta; produces lipid mediators and induces cell death, while lysophosphatidylserine generated by iPLA(2)& beta; induces necrotic cardiomyocyte death through GPR34, leading to cardiac dysfunction in pressure-overloaded mouse hearts.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Dongchen An, Steve Peigneur, Jan Tytgat
Summary: The coupling of cannabinoid receptors, CB1 and CB2, to G protein-coupled inward rectifier potassium channels, GIRK1 and GIRK2, modulates neuronal excitability in the human brain. WIN55,212-2, a non-selective agonist of CB1 and CB2, activates CB1 and CB2 at low concentrations and blocks GIRK1/2 at high concentrations.
Article
Cell Biology
Weiyuan Huang, Yue Ke, Jianping Zhu, Shuai Liu, Jin Cong, Hailin Ye, Yanwu Guo, Kewan Wang, Zhenhai Zhang, Wenxiang Meng, Tian-Ming Gao, Heiko J. Luhmann, Werner Kilb, Rongqing Chen
Summary: Depolarization-induced shunting inhibition (DShI) mediates non-synaptic, neuronal intrinsic short-term plasticity, which suppresses action potential generation and postsynaptic responses. The TRESK channel significantly contributes to DShI and may represent a therapeutic target for antiepileptic drugs.
Article
Materials Science, Multidisciplinary
Ben Chen, Jing Yu, Rui Wang, Xianggong Zhang, Beibei He, Jun Jin, Huanwen Wang, Yansheng Gong
Summary: In this study, a g-C3N4-Cu2O-TiO2 photocatalyst with a novel three-dimensional ordered macroporous (3DOM) structure was prepared successfully. The unique porous structure enabled higher specific surface area and active sites, leading to improved photocatalytic performance. The double p-n heterojunction and robust porous structure of g-C3N4-Cu2O-TiO2 contributed to enhanced photoactivity, with promising implications for developing cost-effective heterojunction photocatalysts.
SCIENCE CHINA-MATERIALS
(2022)
Article
Biochemistry & Molecular Biology
Alexander V. Mayorov, Bert Willis, Antonia Di Mola, Derek Adler, Jennifer Borgia, Olin Jackson, Jie Wang, Yongyi Luo, Lei Tang, Richard J. Knapp, Chandra Natarajan, Michael C. Goodnough, Noam Zilberberg, Lance L. Simpson, Kim D. Janda
ACS CHEMICAL BIOLOGY
(2010)
Article
Genetics & Heredity
Ortal Barel, Stavit A. Shalev, Rivka Ofir, Asi Cohen, Joel Zlotogora, Zamir Shorer, Galia Mazor, Gal Finer, Shareef Khateeb, Noam Zilberberg, Ohad S. Birk
AMERICAN JOURNAL OF HUMAN GENETICS
(2008)
Article
Evolutionary Biology
Adi Kozminsky-Atias, Adi Bar-Shalom, Dan Mishmar, Noam Zilberberg
BMC EVOLUTIONARY BIOLOGY
(2008)
Article
Biophysics
Asi Cohen, Yuval Ben-Abu, Noam Zilberberg
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
(2009)
Article
Biochemistry & Molecular Biology
Adi Kozminsky-Atias, Noam Zilberberg
Article
Biochemistry & Molecular Biology
Asi Cohen, Yuval Ben-Abu, Shelly Hen, Noam Zilberberg
JOURNAL OF BIOLOGICAL CHEMISTRY
(2008)
Article
Biochemistry & Molecular Biology
Laetitia Arzoine, Noam Zilberberg, Ronit Ben-Romano, Varda Shoshan-Barmatz
JOURNAL OF BIOLOGICAL CHEMISTRY
(2009)
Article
Neurosciences
Yifat Segal-Hayoun, Asi Cohen, Noam Zilberberg
MOLECULAR AND CELLULAR NEUROSCIENCE
(2010)
Article
Biochemistry & Molecular Biology
Yuval Ben-Abu, Yufeng Zhou, Noam Zilberberg, Ofer Yifrach
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2009)
Article
Pharmacology & Pharmacy
Eden Arazi, Galit Blecher, Noam Zilberberg
FRONTIERS IN PHARMACOLOGY
(2020)
Article
Neurosciences
Eden Arazi, Galit Blecher, Noam Zilberberg
MOLECULAR AND CELLULAR NEUROSCIENCE
(2020)
Article
Cardiac & Cardiovascular Systems
Max Drabkin, Noam Zilberberg, Sasson Menahem, Wesam Mulla, Daniel Halperin, Yuval Yogev, Ohad Wormser, Yonatan Perez, Rotem Kadir, Yoram Etzion, Amos Katz, Ohad S. Birk
CIRCULATION-GENOMIC AND PRECISION MEDICINE
(2018)
Article
Biochemistry & Molecular Biology
Adi Kominsky-Atias, Erez Somech, Noam Zilberberg
Article
Biochemical Research Methods
Asi Cohen, Noam Zilberberg
JOURNAL OF NEUROSCIENCE METHODS
(2006)