Article
Multidisciplinary Sciences
Kirin D. Gada, Mengmeng Chang, Aishwarya Chandrashekar, Leigh D. Plant, Sami F. Noujaim, Diomedes E. Logothetis
Summary: G-protein-gated inwardly rectifying potassium (GIRK) channel activity is regulated by phosphatidylinositol-4,5-bisphosphate (PI 4,5P(2)), and PKC epsilon plays a role in the activation of GIRK channels in cardiac atrial cells and human stem cell-derived atrial cardiomyocytes. PKC epsilon enhances the interaction between GIRK4 and GIRK1/4 with PIP2, leading to increased channel activity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Chemistry, Multidisciplinary
Chen Zhao, Huanting Wang, Huacheng Zhang
Summary: Artificial ion channels mimicking the intelligent gating functions of biological ion channels are crucial for sensing, delivery, and separation. Advances have been made in fabricating bio-inspired switchable ion channels, which show improved gating features and can be smartly regulated using various physical and chemical stimuli.
MATERIALS CHEMISTRY FRONTIERS
(2021)
Article
Biology
Joseph W. Nors, Shipra Gupta, Marcel P. Goldschen-Ohm
Summary: The study investigates the role of the α(1)M2-M3 linker in the modulation of BZDs on pore opening, identifying the α(1)V279A mutation that significantly increases the energetic contribution of BZDs to pore opening. Other linker mutations have little effect on BZD efficiency but generally impair unliganded pore opening.
Article
Chemistry, Multidisciplinary
Xiuqin Yu, Cuiyan Li, Jianhong Chang, Yujie Wang, Weifeng Xia, Jinquan Suo, Xinyu Guan, Valentin Valtchev, Yushan Yan, Shilun Qiu, Qianrong Fang
Summary: Functionalized covalent organic frameworks (COFs) can serve as an efficient nanofluidic platform for intelligent modulation of ion transport. The materials exhibit outstanding selective ion transmission performance with high gating ratios, among the highest reported in solid-state nanochannels. The research also demonstrates the high tunability, selectivity, and recyclability of ion transport in COFs.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Physics, Multidisciplinary
Lukasz Machura, Agata Wawrzkiewicz-Jalowiecka, Monika Richter-Laskowska, Paulina Trybek
Summary: The study explores the complexity of empirical data on ionic currents flowing through a single channel in a biological membrane. Simulated data reveal the significant influence of temperature and conformational changes on the complexity of the currents, which are difficult to control experimentally.
Article
Multidisciplinary Sciences
Zhengshan Hu, Xiangdong Zheng, Jian Yang
Summary: The study presents the structures of the cGMP-activated human cone photoreceptor CNGA3/CNGB3 channel in different states. The findings reveal the conformational trajectory of the channel and provide an expanded framework for studying CNG properties and channelopathy.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Edyta Glogowska, Malika Arhatte, Franck C. Chatelain, Florian Lesage, Aimin Xu, Carsten Grashoff, Dennis E. Discher, Amanda Patel, Eric Honore
Summary: The study demonstrates that Piezo1/2 channels can increase the current amplitude of TREK/TRAAK channels, slow down their activation/deactivation rates, and remove their inactivation upon mechanical stimulation. This regulation is mainly achieved through a local depletion of membrane cholesterol, occurring in mouse fibroblasts and affecting wound healing speed.
Article
Neurosciences
Jing Xue, Yan Han, Weizhong Zeng, Yan Wang, Youxing Jiang
Summary: This study reveals the structural mechanism of ligand gating in the human rod CNGA1 channel, including channel conformation and ion binding sites, providing insights into Ca2+ blockage and permeation in CNG channels.
Article
Multidisciplinary Sciences
Grigory Maksaev, Michael Bruendl-Jirout, Anna Stary-Weinzinger, Eva-Maria Zangerl-Plessl, Sun-Joo Lee, Colin G. Nichols
Summary: The authors introduced negative charges in Kir2.2 channels, resulting in pH-dependent sub-conductances. Molecular dynamics simulations show that protonation leads to step-wise alterations of ion pooling and conductance, appearing as gated substates. Single-channel recordings reveal pH-dependent subconductance behaviors.
NATURE COMMUNICATIONS
(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)
Review
Biochemistry & Molecular Biology
Valerij S. Sokolov, Vladimir V. Cherny, Artem G. Ayuyan, Thomas E. DeCoursey
Summary: H(V)1 channels, resembling the voltage-sensing domain of other voltage-gated ion channels, feature a unique Delta pH dependent gating mechanism that regulates channel opening by pH on both sides of the membrane. Two mechanisms, the countercharge mechanism and the electrostatic mechanism, are proposed to contribute to this Delta pH dependent gating. Both mechanisms are likely to operate together to regulate the gating of H(V)1 channels.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2021)
Review
Medicine, Research & Experimental
Yong S. Wang, Tian Y. Qiu, Qiang Fu, Si Q. Xiong, Ze Z. Wang, Ming F. Lu, Jian H. Yang, Zhen Z. Hu
Summary: This article summarizes the signal transduction mechanisms of GABA(B) receptors and their role in synaptic strength and plasticity. It also explores the association between GABA(B) receptors and neuropsychiatric conditions. The research is important for designing therapeutic strategies and improving prognosis rates.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Physiology
Luisa Maria Rosaria Napolitano, Vincent Torre, Arin Marchesi
Summary: Cyclic nucleotide-gated (CNG) channels play a crucial role in signal transduction in sensory modalities, with functional properties different from voltage-gated potassium channels despite structural similarities. Recent high-resolution structures of intact CNG channels have advanced the understanding of their activation mechanisms.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Daohua Jiang, Richard Banh, Tamer M. Gamal El-Din, Lige Tonggu, Michael J. Lenaeus, Regis Pomes, Ning Zheng, William A. Catterall
Summary: Research has uncovered the open-state structure of the sodium channel Na(v)1.5, revealing the mechanism of pore opening by blocking fast inactivation. This provides crucial molecular-level insights into the initiation of heartbeat.
Review
Virology
Siobhan Gargan, Nigel J. Stevenson
Summary: Viroporins are a family of important viral proteins that regulate viral infection and replication in host cells, as well as contribute to viral immune evasion. Studies on viroporins are essential for the development of novel antiviral therapies.
Article
Chemistry, Medicinal
Kirsten Yakoub, Sascha Jung, Christian Sattler, Helen Damerow, Judith Weber, Annika Kretzschmann, Aylin S. Cankaya, Markus Piel, Frank Roesch, Anne S. Haugaard, Bente Frolund, Tanja Schirmeister, Hartmut Lueddens
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Biochemistry & Molecular Biology
Christian Sattler, Ralf Schmauder, Tina Schwabe, Andrea Schweinitz, Christopher Unzeitig, Frank Schwede, Maik Otte, Klaus Benndorf
JOURNAL OF NEUROCHEMISTRY
(2020)
Article
Physiology
Florian Walther, Dominic Feind, Christian vom Dahl, Christoph Emanuel Mueller, Taulant Kukaj, Christian Sattler, Georg Nagel, Shiqiang Gao, Thomas Zimmer
JOURNAL OF GENERAL PHYSIOLOGY
(2020)
Article
Biophysics
Christopher Pfleger, Jana Kusch, Mahesh Kondapuram, Tina Schwabe, Christian Sattler, Klaus Benndorf, Holger Gohlke
Summary: The opening of HCN channels is controlled by membrane hyperpolarization and the binding of cyclic nucleotides to the CNBD domain. Through a rigidity-theory-based approach, researchers identified different pathways within the CL-CNBD that modulate cAMP-binding responses. Results suggest the presence of functionally relevant submodules within and across structurally discernible subunits in HCN channels.
BIOPHYSICAL JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Milica Gusic, Klaus Benndorf, Christian Sattler
Summary: Our study reveals that each occupied binding site contributes to channel activation in P2X7 receptors. While the occupation of a single binding site can activate the channels, three bound ligands maximally stabilize the open state, suggesting a stepwise activation process for P2X7 receptors.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Jana Schirmeyer, Sabine Hummert, Thomas Eick, Eckhard Schulz, Tina Schwabe, Gunter Ehrlich, Taulant Kukaj, Melanie Wiegand, Christian Sattler, Ralf Schmauder, Thomas Zimmer, Nisa Kosmalla, Jan Munch, Michele Bonus, Holger Gohlke, Klaus Benndorf
Summary: This study on olfactory CNG channels reveals the specific mutual control of individual subunits through analyzing the thermodynamics of microscopic cooperativity for ligand binding. The Gibbs free energy calculations show that preoccupation of each subunit increases the affinity of other subunits, and the equilibrium constants of closed-open isomerizations systematically increase with progressive liganding.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
Christian Sattler, Klaus Benndorf
Summary: P2X receptors are trimeric nonselective cation channels gated by ATP. They play important roles in various physiological processes and are challenging pharmacological targets. The determination of their crystal and cryo-EM structures has provided a basis for understanding their functional and biochemical data, while electrophysiological characterization in conjunction with optical methods has revealed their structure-function relationships.
PURINERGIC SIGNALLING
(2022)
Article
Physiology
Klaus Benndorf, Thomas Eick, Christian Sattler, Ralf Schmauder, Eckhard Schulz
Summary: Benndorf et al. introduce a strategy to analyze the functionality of heteromeric ligand-gated ion channels by combining subunit concatenation, mutagenesis, and global fit strategies with Markov models. Their approach enables them to determine multiple functional parameters of individual subunits with high precision.
JOURNAL OF GENERAL PHYSIOLOGY
(2022)
Article
Biology
Mahesh Kondapuram, Benedikt Frieg, Sezin Yueksel, Tina Schwabe, Christian Sattler, Marco Lelle, Andrea Schweinitz, Ralf Schmauder, Klaus Benndorf, Holger Gohlke, Jana Kusch
Summary: In this study, the crucial role of residue K464 of the C-linker in stabilizing the closed state of the mHCN2 channel was demonstrated through mutagenesis, patch-clamp technique, confocal patch-clamp fluorometry, and molecular dynamics simulations. The K464E mutation disrupted the interactions between subunits, favoring a pre-activated state of the channel.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemical Research Methods
Jana Schirmeyer, Thomas Eick, Eckhard Schulz, Sabine Hummert, Christian Sattler, Ralf Schmauder, Klaus Benndorf
Summary: Cyclic nucleotide-gated ion channels in olfactory sensory neurons have three types of homologous subunits. The study found that the activation process of the channels is cooperatively influenced by the subunits, while the energy required for channel opening is independent of subunit cooperativity.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Biology
Taulant Kukaj, Christian Sattler, Thomas Zimmer, Ralf Schmauder, Klaus Benndorf
Summary: FRET and confocal patch-clamp fluorometry were used to analyze glutamate-induced conformational changes and dimerization of mGluR 1-8 homo- and heterodimers in oocytes. The study found that 5 out of 8 homodimeric receptors and 11 out of 28 heterodimers demonstrated characteristic glutamate-induced kinetics. Glutamate-responsive heterodimers were identified within each group and between groups I and II, as well as II and III, but not between groups I and III. Heterodimers showed heterogeneous activation and deactivation kinetics.
COMMUNICATIONS BIOLOGY
(2023)