Article
Cell Biology
Rebecca Jarvis, Shu Fun Josephine Ng, Anna J. Nathanson, Ross A. Cardarelli, Krithika Abiraman, Fergus Wade, Aidan Evans-Strong, Marina P. Fernandez-Campa, Tarek Z. Deeb, Joshua L. Smalley, Tanguy Jamier, Ian K. Gurrell, Lisa McWilliams, Aarti Kawatkar, Leslie C. Conway, Qi Wang, Roland W. Burli, Nicholas J. Brandon, Iain P. Chessell, Aaron J. Goldman, Jamie L. Maguire, Stephen J. Moss
Summary: Activation of KCC2 can reduce benzodiazepine-resistant seizures and decrease associated neuronal damage.
CELL REPORTS MEDICINE
(2023)
Article
Neurosciences
Philip Hampel, Marie Johne, Bjoern Gailus, Alexandra Vogel, Alina Schidlitzki, Birthe Gericke, Kathrin Toellner, Wiebke Theilmann, Christopher Kaeufer, Kerstin Roemermann, Kai Kaila, Wolfgang Loescher
Summary: The study investigated the effects of NKCC1 expression on seizures and epilepsy using KO and WT mice. Results showed that while NKCC1 deficiency did not affect the induction and progression of epilepsy, it led to a more severe epileptic phenotype.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Biology
Sensen Zhang, Jun Zhou, Yuebin Zhang, Tianya Liu, Perrine Friedel, Wei Zhuo, Suma Somasekharan, Kasturi Roy, Laixing Zhang, Yang Liu, Xianbin Meng, Haiteng Deng, Wenwen Zeng, Guohui Li, Biff Forbush, Maojun Yang
Summary: In this study, the cryo-electron microscopy structures of the two neuronal cation-chloride cotransporters human NKCC1 and mouse KCC2 were presented, identifying essential residues for ion transport. The study proposes mechanisms by which phosphorylation regulates the activity of these cation-chloride cotransporters.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Caroline Neumann, Lena Lindtoft Rosenbaek, Rasmus Kock Flygaard, Michael Habeck, Jesper Lykkegaard Karlsen, Yong Wang, Kresten Lindorff-Larsen, Hans Henrik Gad, Rune Hartmann, Joseph Anthony Lyons, Robert A. Fenton, Poul Nissen
Summary: The sodium-potassium-chloride transporter NKCC1 is a crucial protein involved in ion uptake across plasma membranes. This study presents the cryo-electron microscopy structure of human NKCC1 and provides insights into its functional mechanism. The findings have implications for understanding the structure-function relationship of NKCC1 and other related proteins.
Article
Genetics & Heredity
Monis Bilal Shamsi, Mohamed Saleh, Makki Almuntashri, Essa Alharby, Manar Samman, Roy W. A. Peake, Fatima M. Al-Fadhli, Ali Alasmari, Eissa A. Faqeih, Naif A. M. Almontashiri
Summary: Heterozygous pathogenic variants in SLC12A2 have been linked to nonsyndromic hearing loss, while homozygous loss-of-function variants have been associated with syndromic intellectual disability. Variants in the c-terminal domain of the SLC12A2 gene seem to play a critical role in the functioning of the encoded co-transporter protein. The study provides additional confirmation of the autosomal recessive SLC12A2 disease.
JOURNAL OF HUMAN GENETICS
(2021)
Review
Geriatrics & Gerontology
Pavel A. Kipnis, Shilpa D. Kadam
Summary: Epilepsy is a complex disorder associated with various neurological conditions, causing ongoing seizures for millions of patients worldwide despite optimal treatment. Refractory epilepsy poses a challenge for effective management, especially in cases of early-life seizures like those caused by perinatal hypoxic ischemic encephalopathy.
Review
Neurosciences
Werner Kilb
Summary: This article discusses the effect of GABA on neuronal excitability, the complex spatiotemporal interaction between GABAergic and glutamatergic inputs, and mechanisms influencing [Cl-](i) beyond Cl- transporters expression. Research suggests that during early developmental stages, GABA can act as an inhibitory neurotransmitter.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Oncology
Jie Wang, Wangrui Liu, Wenhao Xu, Baofeng Yang, Mingzhu Cui, Zhen Li, Hailiang Zhang, Chuntao Jin, Huanzhou Xue, Jiaqiang Zhang
Summary: This study comprehensively investigated the molecular and clinical role of CCCs, and illustrated the significant association among KCC2/NKCC1 expression, DNA variation profiles, prognosis, and TME of pan-cancer.
FRONTIERS IN ONCOLOGY
(2022)
Review
Clinical Neurology
Yehezkel Ben-Ari, Eric Delpire
Summary: The study shows that phenobarbital and midazolam can reduce neonatal seizures following birth asphyxia, but their effectiveness is dependent on the timing of administration; in contrast, the chloride importer antagonist has no effect on reducing seizures. However, the efficacy of drugs on seizures may be influenced by recurrent seizures.
Review
Pharmacology & Pharmacy
Shihan Salihu, Nur Farah Meor Azlan, Sunday Solomon Josiah, Zhijuan Wu, Yun Wang, Jinwei Zhang
Summary: The circadian system is controlled by the suprachiasmatic nucleus (SCN), and GABAergic neurons play a role in regulating the circadian rhythms by controlling chloride levels. Recent studies have shown excitatory responses in this area due to an increase in chloride ion levels. Changes in the expression and activity of the cation-chloride cotransporters NKCC1 and KCC2 in SCN neurons are associated with circadian rhythms.
ASIAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Review
Clinical Neurology
Wolfgang Loescher, Kai Kaila
Summary: This response corrects the inaccurate descriptions of the model and data in a recent study on the pharmacology of neonatal seizures in a novel rat model of birth asphyxia by Ben-Ari and Delpire. The authors also address the implications of bumetanide actions on neurons in other brain disorders due to its poor brain penetration and wide cellular expression patterns of the target protein NKCC1.
Article
Cell Biology
Egor Byvaltcev, Mahraz Behbood, Jan-Hendrik Schleimer, Thomas Gensch, Alexey Semyanov, Susanne Schreiber, Ulf Strauss
Summary: Extracellular potassium [K+]o elevation during synaptic activity retrogradely modifies presynaptic release and astrocytic uptake of glutamate. Hence, local K+ clearance and replenishment mechanisms are crucial regulators of glutamatergic transmission and plasticity. Based on recordings of astrocytic inward rectifier potassium current IKir and K+-sensitive electrodes as sensors of [K+]o as well as on in silico modeling, we demonstrate that the neuronal K+-Cl- co-transporter KCC2 clears local perisynaptic [K+]o during synaptic excitation by operating in an activity-dependent reversed mode.
Article
Biochemistry & Molecular Biology
Phu C. Duong, Tobias C. McCabe, Grace F. Riley, Heather L. Holmes, Peter M. Piermarini, Michael F. Romero, Christopher M. Gillen
Summary: Dipteran insects have genes that code for two different Na+-dependent cation-chloride cotransporter (CCC) paralogs, and their function and localization differ.
INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2022)
Review
Clinical Neurology
Brennan J. Sullivan, Shilpa D. Kadam
Summary: BDNF plays a critical role in neuronal development and synapse formation, with excessive signaling potentially contributing to refractory neonatal seizures.
PEDIATRIC NEUROLOGY
(2021)
Article
Cell Biology
Samu N. Kurki, Rakenduvadhana Srinivasan, Jens Laine, Mari A. Virtanen, Tommi Ala-Kurikka, Juha Voipio, Kai Kaila
Summary: Acute neuroinflammation leads to hyperexcitability in dentate gyrus (DG) neurons, caused by disruption of neuronal chloride regulation and loss of GABAergic inhibition, resulting in cognitive impairment.