Article
Pharmacology & Pharmacy
Hao Wang, Di Ma, Xiaojuan Zhu, Panyue Liu, Shuai Li, Bo Yu, Hong Yang
Summary: Nimodipine effectively inhibits TMEM16A/CaCCs by reducing transmembrane Ca2+ influx and interacting directly with TMEM16A, explaining its relaxing effects on intestinal and aortic smooth muscle contraction.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2021)
Review
Multidisciplinary Sciences
Weiliang Bai, Mei Liu, Qinghuan Xiao
Summary: TMEM16A is a calcium-activated chloride channel protein that plays diverse roles in inflammation, including promoting the release of inflammatory mediators, increasing vascular permeability, and sensing pain. In different inflammatory diseases, TMEM16A exerts varied pathological effects in a cellular environment-dependent manner.
JOURNAL OF ADVANCED RESEARCH
(2021)
Review
Pharmacology & Pharmacy
Yani Liu, Zongtao Liu, KeWei Wang
Summary: ANO1 gene encodes a Ca2+ activated Cl- channel critical for physiological functions, with abnormal expression or dysfunction linked to various diseases. The lack of specific modulators hinders the validation of ANO1 as a therapeutic target.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Pharmacology & Pharmacy
Chao Qu, Xin Guan, Chang Li, Xiaojuan Zhu, Tonghui Ma, Hongyan Li, Bo Yu, Hong Yang
Summary: The sesquiterpene lactones, alantolactone (AL) and isoalantolactone (iAL), have been found to inhibit CFTR and CaCCs activities in intestinal epithelial cells, leading to a reduction in fluid losses and intestinal motility and a decrease in watery diarrhea caused by rotavirus infection. These compounds may hold potential for the development of new treatments for rotaviral secretory diarrhea.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Daniel Leon-Aparicio, Jorge Arreola, Patricia Perez-Cornejo, Alfredo Sanchez-Solano
Summary: The study shows that oleic acid irreversibly blocks the TMEM16A chloride channel in a dose- and voltage-dependent manner, possibly through an allosteric mechanism. This blockage is intensified by increasing the extracellular anion concentration and is independent of voltage for certain pore mutants.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2022)
Editorial Material
Biology
Thomas Kaas, Jana Nerlich, Stefan Hallermann
Summary: A new study reveals the involvement of intermediate gating states in calcium channels, shedding light on how analogue postsynaptic potentials affect neurotransmitter release.
Article
Biochemistry & Molecular Biology
Woori Ko, Byung-Chang Suh
Summary: The membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PI(4,5)P-2) selectively modulates the gating of the TMEM16A(ac) channel in an agonistic manner, leading to the upregulation of TMEM16A(ac) functions in physiological conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Tianyu Wang, Hui Wang, Fan Yang, Kuan Gao, Shuya Luo, Lichuan Bai, Ke Ma, Mei Liu, Shuwei Wu, Huijie Wang, Zaixing Chen, Qinghuan Xiao
Summary: This study revealed a new anticancer mechanism of honokiol by inhibiting cell proliferation through targeting Ano1 Ca2+-activated Cl- channels. Honokiol more potently inhibited Ano1 currents compared to Ano2 currents, with three critical amino acids (R429, K430, and N435) identified for honokiol-induced Ano1 inhibition.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Marta Martini, Giorgio Rispoli
Summary: Some sensory disorders in hearing, vestibular, and vision can be attributed to voltage-gated Ca2+ channels in sensory cells. In this study, the Na+ current flowing through L- and R-type Ca2+ channels in labyrinth hair cells was investigated. The activation and deactivation of the Na+ current in L-type channels were affected by low Ca2+ concentration, resulting in increased current amplitude. The R-type Na+ current was partially blocked by nifedipine and its current amplitude increased in low Ca2+ condition. Furthermore, the selectivity filter of R channels was less affected by external Ca2+ compared to L channels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Ke Ma, Sitong Liu, Hongyue Liang, Guan Wang, Tianyu Wang, Shuya Luo, Kuan Gao, Hui Wang, Mei Liu, Lichuan Bai, Qinghuan Xiao
Summary: This study reveals a novel mechanism of cholesterol-mediated TMEM16A inhibition, by which cholesterol reduces TMEM16A expression via DNMT1-mediated methylation and directly inhibits channel activities. TMEM16A channel inhibition promotes endothelial cell angiogenesis.
JOURNAL OF ADVANCED RESEARCH
(2021)
Review
Physiology
Bernard T. Drumm, Keith D. Thornbury, Mark A. Hollywood, Gerard P. Sergeant
Summary: Urinary continence is maintained by the contracture of urethral sphincters, including the role of Ano1 channels expressed in urethral ICC in increasing smooth muscle excitability. However, the specific role of urethral Ano1 channels remains unclear due to differences in species and experimental approaches. Clarifying this situation is crucial for developing new treatments for urinary incontinence.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Takahisa Suzuki, Yoshiaki Suzuki, Kiyofumi Asai, Yuji Imaizumi, Hisao Yamamura
Summary: Hypoxia upregulates the expression of TMEM16A and increases whole-cell Cl-Ca currents, leading to cell proliferation and enhanced endothelial permeability, which can be attenuated by Cl-Ca channel blockers or TMEM16A siRNA. These findings provide insights into the pathological role of TMEM16A Cl-Ca channels in the BBB during cerebral ischemia.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2021)
Article
Chemistry, Medicinal
Juan Antonio Contreras Vite, Carlos Vega Valle, Happi Biekeu Mbem, Sarah-Maude Boivin, Robert Dumaine
Summary: Lamotrigine is commonly used for treating bipolar disorder and epilepsy. The US FDA has recently issued a warning regarding the drug's potential to cause conduction anomalies and Brugada syndrome in epileptic patients. In this study, researchers used patch clamp technique on rat cardiomyocytes to investigate the effect of Lamotrigine on cardiac sodium current (I-Na). The results showed that Lamotrigine inhibited I-Na peak amplitude, reduced cardiac excitability, and prolonged the action potential refractory period in epileptic rats.
Article
Biochemistry & Molecular Biology
Annalisa Bernareggi, Martina Zangari, Andrew Constanti, Paola Zacchi, Violetta Borelli, Alessandro Mangogna, Paola Lorenzon, Giuliano Zabucchi
Summary: This study investigates the effect of crocidolite asbestos fibers on chloride conductance in Xenopus oocyte cell membranes. The results show that exposure to asbestos enhances chloride currents in the membranes, and this enhancement is influenced by calcium levels and specific blockers of TMEM16A Ca2+-activated chloride channels.
Review
Biochemistry & Molecular Biology
Wanying Ji, Donghong Shi, Sai Shi, Xiao Yang, Yafei Chen, Hailong An, Chunli Pang
Summary: This review discusses the calcium sensing sites and activation properties of TMEM16A, helping to understand the structure-function relationship of TMEM16A and providing insights for molecular design targeting the TMEM16A channel.
PROTEIN AND PEPTIDE LETTERS
(2021)
Editorial Material
Biochemistry & Molecular Biology
Shihab Shah, Nikita Gamper
Article
Neurosciences
Fan Zhang, Yiying Wang, Yu Liu, Hao Han, Dandan Zhang, Xizhenzi Fan, Xiaona Du, Nikita Gamper, Hailin Zhang
JOURNAL OF NEUROSCIENCE
(2019)
Article
Anesthesiology
Fan Zhang, Sylvain Gigout, Yu Liu, Yiying Wang, Han Hao, Noel J. Buckley, Hailin Zhang, Ian C. Wood, Nikita Gamper
Article
Biochemistry & Molecular Biology
Hongxue Zhang, Hua Zhang, Chanjuan Wang, Yuhong Wang, Ruya Zou, Chenxia Shi, Bingcai Guan, Nikita Gamper, Yanfang Xu
Article
Neurosciences
Min Su, Li Li, Jing Wang, Hui Sun, Ludi Zhang, Chen Zhao, Ying Xie, Nikita Gamper, Xiaona Du, Hailin Zhang
FRONTIERS IN CELLULAR NEUROSCIENCE
(2019)
Article
Biochemistry & Molecular Biology
Dongyang Huang, Sai Shi, Ce Liang, Xiaoyu Zhang, Xiaona Du, Hailong An, Chris Peers, Hailin Zhang, Nikita Gamper
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Shihab Shah, Chase M. Carver, Pierce Mullen, Stephen Milne, Viktor Lukacs, Mark S. Shapiro, Nikita Gamper
Article
Biochemical Research Methods
Miriam E. Hurley, Thomas M. D. Sheard, Ruth Norman, Hannah M. Kirton, Shihab S. Shah, Eleftheria Pervolaraki, Zhaokang Yang, Nikita Gamper, Ed White, Derek Steele, Izzy Jayasinghe
Summary: The study introduces a correlative imaging protocol to visualize the direct relationship between the ubiquitous intracellular second messenger, calcium (Ca2+), and nanoscale patterns of the ryanodine receptor (RyR) Ca2+ channels. By combining total internal reflection fluorescence (TIRF) imaging and DNA-PAINT imaging, the data can be used to visually identify the ensembles of Ca2+ channels that are locally activated during the genesis of cytoplasmic Ca2+ signals.
Article
Cell Biology
Yuan-Ming Tsai, Frederick Jones, Pierce Mullen, Karen E. Porter, Derek Steele, Chris Peers, Nikita Gamper
Article
Neurosciences
Alexandra Hogea, Shihab Shah, Frederick Jones, Chase M. Carver, Han Hao, Ce Liang, Dongyang Huang, Xiaona Du, Nikita Gamper
Summary: Key findings indicate that JPH4 plays a crucial role in the formation of SOCE complex in rat somatosensory neurons, impacting Ca2+ storage and signalling, leading to reduced inflammatory pain responses.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Review
Biochemistry & Molecular Biology
Nikita Gamper, Shihab Shah
Summary: This article briefly reviews the sensory mechanisms in peripheral somatosensory nerves, emphasizing the regulation of ion channel activity through direct molecular interactions with other proteins in multi-protein complexes.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2022)
Article
Cell Biology
Ludi Zhang, Jing Wang, Chenxu Niu, Yu Zhang, Tiantian Zhu, Dongyang Huang, Jing Ma, Hui Sun, Nikita Gamper, Xiaona Du, Hailin Zhang
Summary: The study explores the cellular mechanisms and circuits underlying chronic-pain-induced depression behavior, revealing that chronic pain development is associated with depressive-like behaviors in a mouse model of trigeminal neuralgia. Increased activity of dopaminergic neurons in the midbrain VTA and a glutamatergic projection pathway from Sp5C to VTA play crucial roles in controlling depression-like behavior in the state of chronic neuropathic pain.
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
Biology
Eider Nunez, Frederick Jones, Arantza Muguruza-Montero, Janire Urrutia, Alejandra Aguado, Covadonga Malo, Ganeko Bernardo-Seisdedos, Carmen Domene, Oscar Millet, Nikita Gamper, Alvaro Villarroel, Henry M. Colecraft
Summary: Neuronal K(V)7 channels are highly sensitive to reactive oxygen species, and the S2S3 linker of the voltage sensor plays a crucial role in redox modulation of the channels. Recent structural studies have revealed interactions between this linker and the Ca2+-binding loop of calmodulin, specifically the EF3 hand, which is essential for the signaling. Disrupting Ca2+ binding to EF3 abolishes the oxidation-induced enhancement of K(V)7.4 currents. Furthermore, the loading of EF3 with Ca2+ is critical for the reorientation of the AB fork, which translates the Ca2+ signals.
Review
Pharmacology & Pharmacy
Xiaona Du, Haixia Gao, David Jaffe, Hailin Zhang, Nikita Gamper
BRITISH JOURNAL OF PHARMACOLOGY
(2018)