Article
Physiology
Estefano Pinilla, Ana Sanchez, Maria P. Martinez, Mercedes Munoz, Albino Garcia-Sacristan, Ralf Kohler, Dolores Prieto, Luis Rivera
Summary: This study demonstrates that K(Ca)1.1 and K(Ca)3.1 channels are functionally expressed in the renal vascular endothelium and play a central role in the EDH-mediated relaxation of kidney preglomerular arteries.
Article
Pharmacology & Pharmacy
Gabriele Carullo, Amer Ahmed, Alfonso Trezza, Ottavia Spiga, Antonella Brizzi, Simona Saponara, Fabio Fusi, Francesca Aiello
Summary: In this study, morin derivatives bearing the nitrophenyl moiety of dihydropyridine Ca2+ antagonists were synthesized to increase flavonoid vasorelaxant activity. Among the newly synthesized morin derivatives, penta-acetylated morin-1 was the most efficacious Ca2+ antagonist with a superior vasorelaxant profile compared to the parent compound, and it also stimulated K(C)a1.1 channel current. These findings suggest a new avenue for the synthesis of valuable multi-functional, vasorelaxant morin derivatives capable of targeting pathways underlying hypertension pathogenesis.
BIOCHEMICAL PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Carlos Ancaten-Gonzalez, Ignacio Segura, Rosangelina Alvarado-Sanchez, Andres E. Chavez, Ramon Latorre
Summary: BK channels are large conductance potassium channels that play crucial roles in regulating neuronal excitability and synaptic communication in the brain. Their dysfunction has been implicated in various neurological disorders. Here, we discuss the physiological importance of BK channels and their contribution to the pathophysiology of different neurological disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Shuxian Huang, Tingting Chen, Qian Suo, Rubing Shi, Haroon Khan, Yuanyuan Ma, Yaohui Tang, Guo-Yuan Yang, Zhijun Zhang
Summary: The activation of BK channels in microglia promotes microglial phagocytosis and benefits neurological recovery after ischemic stroke, suggesting BK channels as a potential therapeutic target for acute stage of ischemic stroke therapy.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Chemistry, Medicinal
Gabriele Carullo, Simona Saponara, Amer Ahmed, Beatrice Gorelli, Sarah Mazzotta, Alfonso Trezza, Beatrice Gianibbi, Giuseppe Campiani, Fabio Fusi, Francesca Aiello
Summary: The labdane scaffold presents a valuable starting point for the development of new vasorelaxant agents. The study reveals the regulatory effects of labdane-type compounds on ion channels and provides a molecular basis for their activity.
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
Xiao Qian, Yong-hui Wu, Yuan-yuan Che, Wei Zhao, Long-fei Shu, Jie Zhu, Yu-hai Wang, Tao Chen
Summary: This study demonstrated that mGluR5 plays a protective role in spinal cord ischemia-reperfusion injury (SCIRI) through modulation of BK channels.
NEUROCHEMISTRY INTERNATIONAL
(2021)
Article
Physiology
Merouann Kassa, Jonathan Bradley, Abdelali Jalil, Isabel Llano
Summary: Using optical activation, this study reveals that neuronal activity in the cerebellar cortex can be increased but also paused after the stimulation. The post-stimulation silencing is likely due to the activation of specific potassium channels.
JOURNAL OF GENERAL PHYSIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Yanjun Guo, Cheng Lu, Luyun Zhang, Hanxing Wan, Enlai Jiang, Yao Chen, Hui Dong
Summary: The study found that nutrients induce endothelium-dependent vasorelaxation in mesenteric arterioles through hyperosmotic action, with glucose stimulating Ca2+ influx through TRPV1 channels. This pathway could be a potential target for gastrointestinal diseases like chronic colitis and mesenteric ischemia.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Guohui Zhang, Xianjin Xu, Zhiguang Jia, Yanyan Geng, Hongwu Liang, Jingyi Shi, Martina Marras, Carlota Abella, Karl L. Magleby, Jonathan R. Silva, Jianhan Chen, Xiaoqin Zou, Jianmin Cui
Summary: Researchers have discovered a compound, BC5, that interacts with the CTD-VSD interface and specifically modulates the Ca2+ dependent activation mechanism. BC5 can activate the channel in the absence of Ca2+ binding, but Ca2+ binding inhibits BC5 effects. This study reveals the importance of the CTD-VSD interaction in the Ca2+ activation mechanism and provides insights for allosteric agonists to modulate BK channel activation.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Vivian Gonzalez-Perez, Pedro L. Martinez-Espinosa, Monica Sala-Rabanal, Nikhil Bharadwaj, Xiao-Ming Xia, Albert C. Chen, David Alvarado, Jenny K. Gustafsson, Hongzhen Hu, Matthew A. Ciorba, Christopher J. Lingle
Summary: Y goblet cells (GCs) in the intestinal epithelium play a key role in mucosal homeostasis by producing and secreting MUC2. The association between LRRC26 and BK channels is crucial for maintaining intestinal mucosal function.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Immunology
Shuai Hu, Runhong Han, Long Chen, Weisong Qin, Xiaodong Xu, Jingsong Shi, Xiaodong Zhu, Mingchao Zhang, Caihong Zeng, Zheng Tang, Hao Bao, Zhihong Liu
Summary: Upregulated LRRC55 promotes BK channel activation and aggravates cell injury in podocytes in FSGS, DN, and MN. LRRC55 inhibition may represent a new therapeutic approach for podocyte injury.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Physiology
Alexandre G. Vouga, Michael E. Rockman, Jiusheng Yan, Marlene A. Jacobson, Brad S. Rothberg
Summary: The drug loperamide has been found to inhibit the activity of large-conductance Ca2+-activated K+ (BK) channels, which may contribute to its therapeutic effects.
JOURNAL OF GENERAL PHYSIOLOGY
(2021)
Article
Neurosciences
Fei Luo, Ting Wang, Jun-yong Deng, Xiao-dan Luo
Summary: Orexin, a neuropeptide synthesized in the hypothalamus, modulates brain activity and is involved in psychiatric disorders. This study found that orexin enhances GABAergic transmission onto mPFC pyramidal neurons by inhibiting inward rectifier K+ channels on Sst interneurons, further depolarizing the interneurons and increasing Ca2+ influx through T-type Ca2+ channels.
EXPERIMENTAL NEUROLOGY
(2023)
Editorial Material
Neurosciences
Hugo G. Marques, Pedro L. Castelhanito, Megan R. Carey
Summary: A recent study has identified a mechanistic pathway by which norepinephrine alters cerebellar Purkinje output to trigger attacks in a mouse model of EA2, and a pharmacological intervention that effectively reduces them.
TRENDS IN NEUROSCIENCES
(2022)
Article
Physiology
T. Li, G. Di Stefano, G. S. Raza, I Sommerer, B. Riederer, D. Roemermann, X. Tan, Q. Tan, P. Pallagi, M. Hollenbach, K-H Herzig, U. Seidler
Summary: Slc26a9 is primarily expressed in pancreatic ducts in mice, and its deletion results in reduced pancreatic fluid secretion and impaired glucose tolerance, especially in female mice. These findings highlight the importance of Slc26a9 in pancreatic physiology.
Article
Physiology
Jean-Claude Kresse, Henricus A. M. Mutsaers, Michael Schou Jensen, Stine Julie Tingskov, Mia Gebauer Madsen, Lene N. Nejsum, Helle Praetorius, Rikke Norregaard
Summary: This study evaluated the role of the PGE(2)-EP1 receptor in renal fibrosis and found that EP1 receptor inhibition can attenuate fibrogenesis, suggesting it as a promising therapeutic target.
Article
Physiology
Samuel L. Svendsen, Simon Kornvig, Peder Berg, Iben S. Jensen, Isabela B. B. A. de Araujo, Casper K. Larsen, Jens Leipziger, Mads Sorensen
Summary: K+-induced diuresis involves desensitization of the collecting duct to AVP.
Editorial Material
Physiology
Helle Praetorius, William E. Louch
Article
Multidisciplinary Sciences
Jennifer Kelly, Miran Al-Rammahi, Kristian Daly, Paul K. Flanagan, Arun Urs, Marta C. Cohen, Gabriella di Stefano, Marcel J. C. Bijvelds, David N. Sheppard, Hugo R. de Jonge, Ursula E. Seidler, Soraya P. Shirazi-Beechey
Summary: Cystic fibrosis is a genetic condition caused by mutations in the CFTR gene that leads to various changes in the small intestine, including the accumulation of dehydrated mucus and altered intestinal motility. These changes in the intestine can lead to gut microbial dysbiosis and affect the normal function of intestinal epithelial cells. The study found that CFTR-null mice and a CF patient had alterations in the mucosa-attached microbiome and epithelial cell profile, including increased inflammation and decreased beneficial bacteria. These findings suggest that the interaction between microbiota and the host may contribute to the development of intestinal CF disease.
SCIENTIFIC REPORTS
(2022)
Review
Physiology
Katerina Nikolovska, Ursula E. Seidler, Christian Stock
Summary: The five plasma membrane Na+/H+ exchanger isoforms in the gastrointestinal tract have distinct characteristics and play important roles in maintaining intestinal homeostasis and disease pathogenesis.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Gastroenterology & Hepatology
Archana Kini, Bei Zhao, Marijana Basic, Urmi Roy, Aida Iljazovic, Ivan Odak, Zhenghao Ye, Brigitte Riederer, Gabriella Di Stefano, Dorothee Roemermann, Christian Koenecke, Andre Bleich, Till Strowig, Ursula Seidler
Summary: This study investigated the changes in microbiota in the colon of mice lacking the SLC26A3 gene, as well as the inflammatory potential and host responses. The results showed that the colon microbiota of SLC26A3-deficient mice was abnormal, but the inflammatory burden in the colon was surprisingly mild, which may be explained by the upregulation of antimicrobial proteins.
Article
Medicine, General & Internal
Lijia Wang, Liping Chen, Xianyuan Wang, Kaiyuan Liu, Ting Li, Yue Yu, Jian Han, Shuai Xing, Jiaxin Xu, Dean Tian, Ursula Seidler, Fang Xiao
Summary: The ResNeXt-101 model established in this study performed better than most clinicians in classifying colonoscopy images as CD, UC, or healthy subjects, suggesting its potential applications in clinical settings.
FRONTIERS IN MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Marc Ferrante, Peter M. Irving, Christian P. Selinger, Geert D'Haens, Tanja Kuehbacher, Ursula Seidler, Savion Gropper, Thomas Haeufel, Sebastiano Forgia, Silvio Danese, Jochen Klaus, Brian G. Feagan
Summary: This study reported the safety, immunogenicity, and efficacy data of intravenous Spesolimab in ulcerative colitis. Spesolimab was well tolerated without unexpected safety concerns, and the safety data were consistent with studies in other inflammatory diseases.
EXPERT OPINION ON DRUG SAFETY
(2023)
Article
Biochemistry & Molecular Biology
Xinjie Tan, Archana Kini, Dorothee Roemermann, Ursula Seidler
Summary: This study explored the potential of using an oral gut-selective NHE3 inhibitor, tenapanor, to reduce the frequency of intestinal obstructive episodes in CFTR-deficient mice. The results showed that oral tenapanor application significantly increased stool water content, reduced gastrointestinal transit time, and prevented obstructive episodes and mucosal inflammation in the mice. This suggests that tenapanor may be a safe and affordable adjunctive therapy for cystic fibrosis patients to alleviate constipation and prevent recurrent DIOS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Nutrition & Dietetics
Nikita Misella Hansen, Peder Berg, Marianne Rix, Manan Pareek, Jens Leipziger, Anne -Lise Kamper, Arne Astrup, Mads Vaarby Sorensen, Louise Salomo
Summary: The objective of this study was to evaluate the effects of the New Nordic Renal Diet (NNRD) on metabolic acidosis and uremic toxins in patients with moderate CKD. The results showed that one week of NNRD effectively improved metabolic acidosis and reduced urinary excretion of uric acid and uremic toxins. These results provide encouragement for further investigations on the long-term renal protection effects of NNRD in patients with CKD.
JOURNAL OF RENAL NUTRITION
(2023)
Article
Physiology
Jacob Rudjord Therkildsen, Stine Julie Tingskov, Michael Schou Jensen, Helle Praetorius, Rikke Norregaard
Summary: P2X(7) receptor plays a regulatory role in late-stage fibrosis by reducing neutrophil-dependent interstitial MMP8 release, resulting in less macrophage infiltration and reduced matrix accumulation.
PHYSIOLOGICAL REPORTS
(2023)
Meeting Abstract
Physiology
J. Qian, Z. Zhou, A. Kini, A. Seidler, B. Riederer, D. Roemermann, G. Gros, A. Vogel, U. Seidler
Meeting Abstract
Physiology
X. Tan, A. Kini, D. Roemermann, U. Seidler
Meeting Abstract
Physiology
E. Tytmonas, A. E. Seidler, G. di Stefano, T. Voigtlaender, T. Hellms, H. Lenzen, U. Seidler, K. Nikolovska