Article
Pharmacology & Pharmacy
Amer Ahmed, Alfonso Trezza, Mariangela Gentile, Eugenio Paccagnini, Alice Panti, Pietro Lupetti, Ottavia Spiga, Sergio Bova, Fabio Fusi
Summary: A study demonstrates that mdivi-1 and dynasore, inhibitors of mitochondrial fission, have vasodilator effects by blocking IBa1.2 and stimulating IKCa1.1 in rat tail artery myocytes. However, the analogue dyngo-4a, while inhibiting mitochondrial fission and stimulating IKCa1.1, does not affect IBa1.2 and potentiates contractions induced by high K+ and phenylephrine. These results caution against using dynasore, mdivi-1, and dyngo-4a as tools to investigate the role of mitochondrial fission in vascular contraction.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Neurosciences
Kelsey C. North, Anna N. Bukiya, Alex M. Dopico
Summary: Pregnenolone constricts middle cerebral arteries independently of neuronal, glial, endothelial, and circulating factors, as well as cell integrity, organelles, membrane cytoarchitecture, and cytosolic signals, through direct inhibition of smooth muscle BK channels.
Article
Multidisciplinary Sciences
Adam Feher, Zoltan Petho, Tibor G. Szanto, Almos Klekner, Gabor Tajti, Gyula Batta, Tibor Hortobagyi, Zoltan Varga, Albrecht Schwab, Gyorgy Panyi
Summary: This study found functional expression of K(Ca)1.1/β3 complex in glioblastoma cells, suggesting its potential diagnostic and therapeutic role in glioblastoma.
SCIENTIFIC REPORTS
(2022)
Article
Physiology
Yanyan Geng, Ping Li, Alice Butler, Bill Wang, Lawrence Salkoff, Karl L. L. Magleby
Summary: This study investigates the molecular basis of a severe developmental and neurological disorder associated with a de novo G375R variant of the BK channel. The results show that the functional heterozygous channels exhibit a diversity of types, including different voltage activation and conductance. The majority of the channels display a gain-of-function in voltage activation and a decrease-of-function in single-channel conductance, with the changes becoming more pronounced as the number of mutant subunits increases.
JOURNAL OF GENERAL PHYSIOLOGY
(2023)
Article
Multidisciplinary Sciences
Lingli He, Jiahui Sun, Yiwei Gao, Bin Li, Yuhang Wang, Yanli Dong, Weidong An, Hang Li, Bei Yang, Yuhan Ge, Xuejun Cai Zhang, Yun Stone Shi, Yan Zhao
Summary: Glutamate-gated kainate receptors interact with NETO2 to form complexes, demonstrating variable stoichiometry in inhibited and desensitized states. NETO2 only accesses two broad faces of kainate receptors and regulates receptor-gating kinetics. The transmembrane helix of NETO2 competes with the amphiphilic H1 helix for interaction with an intracellular cap domain, illustrating how rectification is regulated.
Article
Biochemistry & Molecular Biology
Pedro Martin, Melisa Moncada, Karen Castillo, Federico Orsi, Geronimo Ducca, Jose Manuel Fernandez-Fernandez, Carlos Gonzalez, Veronica Milesi
Summary: Arachidonic acid (AA) directly activates BK channels co-expressed with the auxiliary beta 1 subunit, stabilizing the voltage sensor domain (VSD) on its active configuration and facilitating channel opening transitions when VSD are at rest and CSD are unoccupied. The activation is independent of intracellular Ca2+ concentration and reduced when co-expressed with the Y74A mutant of the beta 1 subunit.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2021)
Article
Pharmacology & Pharmacy
Kelsey C. North, Man Zhang, Aditya K. Singh, Dasha Zaytseva, Alexandria Slayden, Anna N. Bukiya, Alex M. Dopico
Summary: This study reveals that inhibition of calcium/voltage-gated BK channels by membrane cholesterol requires physiological levels of internal calcium (Ca2+) and is selectively linked to high-affinity Ca2+-sensing sites located in the cytosolic tail domain.
MOLECULAR PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Danyang Zhang, Jake F. Watson, Peter M. Matthews, Ondrej Cais, Ingo H. Greger
Summary: This study reveals the structure and active states of AMPAR complexes, demonstrating that TARP-gamma 8 and CNIH2 affect the gating regulation of AMPARs by binding to specific regions of the receptor, thereby promoting the transition to the active-state conformation.
Article
Multidisciplinary Sciences
Serap Erdogmus, Axel R. Concepcion, Megumi Yamashita, Ikjot Sidhu, Anthony Y. Tao, Wenyi Li, Pedro P. Rocha, Bonnie Huang, Ralph Garippa, Boram Lee, Amy Lee, Johannes W. Hell, Richard S. Lewis, Murali Prakriya, Stefan Feske
Summary: The regulatory beta subunit of voltage-gated calcium channels regulates T cell function despite no evidence that these channels were functional within T cells during activation.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Guanxing Chen, Qin Li, Jiusheng Yan
Summary: In this study, the function of the LRR domains in modulation of BK channels by auxiliary gamma subunits was investigated. The results showed that the LRR domain is essential for the all-or-none phenomenon of BK channel modulation by the gamma 1 subunit. Furthermore, N-glycosylation plays a crucial role in the modulation of BK channels by the gamma subunits.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Rajesh Vinnakota, Surbhi Dhingra, Jyoti Kumari, Mohammed Yousuf Ansari, Ekta Shukla, Mayuri Dattatray Nerkar, Janesh Kumar
Summary: This study characterized the biochemical, biophysical, and functional properties of the purified extracellular domain of Neto1, revealing a conformation-dependent interaction with GluK2 receptors. Furthermore, the shape and conformation of Neto1-ECD seem to be altered by calcium ions, indicating a possible role in modulating Neto1 functions.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Anna N. Bukiya, M. Dennis Leo, Jonathan H. Jaggar, Alex M. Dopico
Summary: The activation of BK currents by CLR enrichment requires a prolonged cellular process and is determined by a trafficking-dependent increase in membrane levels of KCNMB1 subunits.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Physiology
Guanxing Chen, Qin Li, Timothy I. Webb, Mark A. Hollywood, Jiusheng Yan
Summary: This study identifies positively charged peptides as modulators of BK channels, and reveals a role for the Ca2+-bowl site and the C-terminal positively charged regions of auxiliary gamma subunits in BK channel modulation. The positively charged peptides and the cationic HIV-1 Tat peptide can shift the voltage-gating of BK channels towards hyperpolarization. The modulatory effects of the synthetic peptides are reduced in the presence of Ca2+ and can be abolished by charge neutralization of the Ca2+-bowl site and high ionic strength.
JOURNAL OF GENERAL PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ye Han, Iredia D. Iyamu, Matthew R. Clutter, Rama K. Mishra, Kyle A. Lyman, Chengwen Zhou, Ioannis Michailidis, Maya Y. Xia, Horrick Sharma, Chi-Hao Luan, Gary E. Schiltz, Dane M. Chetkovich
Summary: Major depressive disorder is a critical public health problem with a high prevalence in the United States. Researchers have discovered that disrupting the interaction between HCN channels and TRIP8b could be a potential therapeutic target for treating cognitive impairment caused by chronic stress.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Eric Gibbs, Emily Klemm, David Seiferth, Arvind Kumar, Serban L. Ilca, Philip C. Biggin, Sudha Chakrapani
Summary: In this study, cryo-EM structures of the α1βGlyR in the presence of an antagonist, agonist, and agonist with a positive allosteric modulator were determined. The structures revealed distinct pore conformations with varying degrees of asymmetry, and the receptors were found to be in closed or desensitized states. Subunit-specific features and characteristics of the extracellular and intracellular domains were also identified. These findings provide a framework for further investigations into the function of this physiologically important channel.
NATURE COMMUNICATIONS
(2023)