Article
Cell Biology
Jiangtao Zhang, Shiqi Liu, Junping Fan, Rui Yan, Bo Huang, Feng Zhou, Tian Yuan, Jianke Gong, Zhu Huang, Daohua Jiang
Summary: In this study, cryoelectron microscopy was used to obtain structures of the Slo2.2 channel in closed, open, and inhibitor-bound form, providing insights into its cation regulation and inhibition. The closed state of Slo2.2 contains multiple K+ and Zn2+ binding sites in the cytoplasmic gating ring domain, which stabilize the closed conformation. The open state reveals Na+-sensitive sites that induce gating ring expansion and rotation upon Na+ binding, leading to inner gate opening. Additionally, a potent inhibitor blocks the pore by binding to a pocket formed by the pore helix and S6 helix. These findings establish a structural framework for studying Slo2.2 channel gating, Na+ sensation, and inhibition.
Article
Biophysics
Ilsbeth G. M. van Herck, Vincent Seutin, Bo H. Bentzen, Neil V. Marrion, Andrew G. Edwards
Summary: The functional properties of two unrelated SK channel inhibitors, apamin and AP14145, in atrial fibrillation treatment are poorly understood. This study investigated their impact on SK channel function and found that both inhibitors induce long-lived channel closures and alter gating kinetics and unitary current. These unique effects are crucial for understanding the functional differences of each inhibitor in the context of cyclical Ca2+-dependent channel activation in vivo.
BIOPHYSICAL JOURNAL
(2023)
Article
Multidisciplinary Sciences
Josef Shin, Lora Kovacheva, Dominique Thomas, Strahinja Stojanovic, Christopher J. Knowlton, Johanna Mankel, Johannes Boehm, Navid Farassat, Carlos Paladini, Joerg Striessnig, Carmen C. Canavier, Gerd Geisslinger, Jochen Roeper
Summary: This study reveals the pacemaker function of the low-threshold L-type calcium channel Ca(v)1.3 in mice and demonstrates its role as a linear amplifier of firing rates for neuronal activity. It also provides evidence that the L-type channel inhibitor isradipine can selectively reduce the firing activity of vulnerable nigrostriatal DA SN neurons at therapeutic concentrations. These findings have important implications for the treatment of Parkinson's disease.
Article
Biology
Dina Simkin, Kelly A. Marshall, Carlos G. Vanoye, Reshma R. Desai, Bernabe Bustos, Brandon N. Piyevsky, Juan A. Ortega, Marc Forrest, Gabriella L. Robertson, Peter Penzes, Linda C. Laux, Steven J. Lubbe, John J. Millichap, Alfred L. George, Evangelos Kiskinis
Summary: Mutations in the KCNQ2 gene result in neonatal epileptic encephalopathy with severe seizures and neurodevelopmental impairments. Patient-derived neurons show specific functional properties that can be replicated in control neurons by chronically inhibiting the M-current. Dyshomeostatic mechanisms exacerbate KCNQ2 loss-of-function in patient iPSC-derived neurons.
Article
Chemistry, Multidisciplinary
Ping Duan, Yaping Wang, Lichuan Chen, Kai Qu, Junyang Liu, Qian-Chong Zhang, Zhong-Ning Chen, Wenjing Hong
Summary: Investigating the correlations of electron transport between multiple channels shows promise for the design of molecule-scale circuits with logic operations. The modulation of electronegativity provides an effective method for controlling electron transport through multiple channels and exploring their interactions. Experimental and theoretical studies suggest that electronegativity has a more significant effect on electron transport in dual-channel structures.
Article
Multidisciplinary Sciences
Lina A. Matschke, Marlene A. Komadowski, Annette Stoehr, Bolam Lee, Martin T. Henrich, Markus Griesbach, Susanne Rinne, Fanni F. Geibl, Wei-Hua Chiu, James B. Koprich, Jonathan M. Brotchie, Aytug K. Kiper, Amalia M. Dolga, Wolfgang H. Oertel, Niels Decher
Summary: This study characterizes the electrophysiological properties of neurons in Parkinson's disease (PD) models and suggests a role of Ca2+-activated K+ (SK) channels in PD by linking changes in LC firing rate to SK channel dysfunction.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Young -Woo Nam, Rajasekharreddy Pala, Naglaa Salem El-Sayed, Denisse Larin-Henriquez, Farideh Amirrad, Grace Yang, Mohammad Asikur Rahman, Razan Orfali, Myles Downey, Keykavous Parang, Surya M. Nauli, Miao Zhang
Summary: Compound 4 selectively potentiates human K(Ca)2.3 channels, increasing flow-induced Ca2+ signaling and cilia length in endothelial cells, with potential implications in vasodilation and ciliopathic hypertension.
ACS CHEMICAL BIOLOGY
(2022)
Article
Anesthesiology
Joel Castro, Jessica Maddern, Andelain Erickson, Ashlee Caldwell, Luke Grundy, Andrea M. Harrington, Stuart M. Brierley
Summary: This study focused on understanding the sensory pathways of vaginal pain and identifying potential molecular targets to modulate vaginal nociceptive signalling. By examining the mechanosensory properties of pelvic afferent nerves innervating the mouse vagina and the expression profile of Na-V channels within these afferents, the study explored how modulation of these channels affects vaginal pain signalling. The findings provide insight into potential approaches for managing dyspareunia related to endometriosis and vulvodynia.
Article
Biochemical Research Methods
Monika Richter-Laskowska, Paulina Trybek, Piotr Bednarczyk, Agata Wawrzkiewicz-Jalowiecka
Summary: Research demonstrates that flavanones, including naringenin, show promise as regulators of the large conductance voltage- and Ca2+- activated K+ channels on the inner mitochondrial membrane, mitoBK. The molecular mechanism of mitoBK-Nar interactions and their effects on conformational dynamics remain unclear. Artificial intelligence methods, such as k-NN and shapelet learning, were used to analyze dwell-time series of mitoBK channels at different voltages and Nar concentrations, revealing stimulus-specific patterns of channel gating and the complex interactions between the channel gate, voltage sensor, and Nar-binding site. In addition, long-range intra-sensor interactions between VSD and the Nar-coordination site were found to play a role in Nar-activation at deeply depolarized membranes.
PLOS COMPUTATIONAL BIOLOGY
(2022)
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
Multidisciplinary Sciences
Yoshiaki Kise, Go Kasuya, Hiroyuki H. Okamoto, Daichi Yamanouchi, Kan Kobayashi, Tsukasa Kusakizako, Tomohiro Nishizawa, Koichi Nakajo, Osamu Nureki
Summary: Mechanisms of modulation of Kv4 channel complexes by auxiliary subunits are central to the physiological function of channels in the brain and heart. The structures of Kv4.2-KChIP1 and Kv4.2-DPP6S complexes reveal that KChIP1 prevents N-type inactivation and stabilizes the S6 conformation, while DPP6S interacts with the S1 and S2 helices to accelerate voltage-dependent movement. KChIP1 and DPP6S do not directly interact with each other in the ternary complex, suggesting two distinct modes of modulation contribute to evoke A-type currents.
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.
Review
Physiology
Karen Bohmwald, Nicolas M. S. Galvez, Catalina A. Andrade, Valentina P. Mora, Jose T. Munoz, Pablo A. Gonzalez, Claudia A. Riedel, Alexis M. Kalergis
Summary: Most cellular functions require ion homeostasis and movement, with calcium playing a crucial role in regulating immune cell functions. Some viruses have evolved mechanisms to modulate intracellular calcium concentrations to increase infectivity and evade the immune system.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Multidisciplinary Sciences
Matthias Schlichting, Shlesha Richhariya, Nicholas Herndon, Dingbang Ma, Jason Xin, William Lenh, Katharine Abruzzi, Michael Rosbash
Summary: Neuromodulation plays a key role in the circadian clock network and sleep regulation in fruit flies. Mutagenesis strategy identified the involvement of dopamine in sleep regulation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Daniel Dautan, Adrienn Kovacs, Tsogbadrakh Bayasgalan, Miguel A. Diaz-Acevedo, Balazs Pal, Juan Mena-Segovia
Summary: CnF and PPN neurons in the MLR demonstrate distinct physiological properties and connectivity patterns, contributing to short-lasting muscle activation and long-lasting muscle tone increase in motor behavior, respectively.
Article
Neurosciences
Kjartan F. Herrik, Arne Mork, Nelly Richard, Christoffer Bundgaard, Jesper F. Bastlund, Inge E. M. de Jong
Article
Neurosciences
Maria Amat-Foraster, Steven C. Leiser, Kjartan F. Herrik, Nelly Richard, Claus Agerskov, Christoffer Bundgaard, Jesper E. Bastlund, Inge E. M. de Jong
Article
Neurosciences
Maria Amat-Foraster, Anders A. Jensen, Niels Plath, Kjartan F. Herrik, Pau Celada, Francesc Artigas
Article
Neurosciences
N. Hovelso, F. Sotty, L. P. Montezinho, P. S. Pinheiro, K. F. Herrik, A. Mork
CURRENT NEUROPHARMACOLOGY
(2012)
Article
Neurosciences
Huifang Ji, Charlotte Hougaard, Kjartan Frisch Herrik, Dorte Strobaek, Palle Christophersen, Paul D. Shepard
EUROPEAN JOURNAL OF NEUROSCIENCE
(2009)
Article
Neurosciences
Jakob K. Dreyer, Kjartan F. Herrik, Rune W. Berg, Jorn D. Hounsgaard
JOURNAL OF NEUROSCIENCE
(2010)
Article
Neurosciences
Katrine Skovgard, Claus Agerskov, Kristi A. Kohlmeier, Kjartan F. Herrik
Article
Pharmacology & Pharmacy
Kjartan F. Herrik, John P. Redrobe, Dorte Holst, Charlotte Hougaard, Karin Sandager-Nielsen, Alexander N. Nielsen, Huifang Ji, Nina M. Holst, Hanne B. Rasmussen, Elsebet O. Nielsen, Dorte Strobaek, Paul D. Shepard, Palle Christophersen
FRONTIERS IN PHARMACOLOGY
(2012)
Article
Neurosciences
Ingeborg H. Hansen, Claus Agerskov, Lars Arvastson, Jesper F. Bastlund, Helge B. D. Sorensen, Kjartan F. Herrik
EUROPEAN JOURNAL OF NEUROSCIENCE
(2019)