Article
Biochemistry & Molecular Biology
Grigori Y. Rychkov, Zeeshan Shaukat, Chiao Xin Lim, Rashid Hussain, Ben J. Roberts, Claudia M. Bonardi, Guido Rubboli, Brandon F. Meaney, Robyn Whitney, Rikke S. Moller, Michael G. Ricos, Leanne M. Dibbens
Summary: The effects of various KCNT1 mutations on the severity of neurological disorders were investigated, and a positive correlation was found between the severity of the disorder and the KCNT1 channel open probability at resting membrane potential. This suggests that gain of function KCNT1 mutations cause epilepsy by increasing resting potassium conductance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemical Research Methods
Adrienn Szabo, Katalin Schlett, Attila Szuecs, Lyle J. Graham, Joseph Ayers, Lyle J. Graham, Joseph Ayers, Lyle J. Graham, Joseph Ayers
Summary: Activity-dependent regulation of intrinsic excitability plays a crucial role in the plasticity of neuronal circuits. The correlation between static firing responses and dynamic firing responses is surprisingly weak, indicating poor predictive power of static responses for estimating firing responses under synaptic inputs. Two intrinsic K-currents mediated by Kv1 and K-ir channels regulate the differential firing responses of neurons with stuttering and delayed firing types.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Razan Orfali, Nora Albanyan
Summary: The Ca2+ ion is widely used as an intracellular signaling molecule, and Ca2+-activated potassium channels have evolved to receive and propagate Ca2+ signals. These channels are activated by increases in cytosolic calcium, which can be caused by Ca2+ influx via permeable channels or Ca2+ release from the endoplasmic reticulum. The Ca2+ sensitivity of these channels allows internal Ca2+ to regulate cell membrane activity. This review discusses the Ca2+ sensitivity of two well-studied groups of Ca2+-sensitive potassium channels: large-conductance Ca2+-activated K+ channels, K(Ca)1.1, and small/intermediate-conductance Ca2+-activated K+ channels, K(Ca)2.x/K(Ca)3.1.
Article
Neurosciences
Cody A. Boyle, Binqi Hu, Kati L. Quaintance, Saobo Lei
Summary: The activation of V-1a vasopressin receptors in the medial nucleus of central amygdala facilitates neuronal excitability primarily by opening TRPC5 channels. Additionally, AVP excitatory effects involve suppressing Kir channels and PLC beta-mediated depletion of PIP2. Intracellular Ca2+ release and PKC activity are not required for V-1a receptor-mediated excitation in CeM neurons.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Article
Chemistry, Multidisciplinary
Shuaiwei Qi, Chenyang Zhang, Hao Yu, Jing Zhang, Tengfei Yan, Ze Lin, Bing Yang, Zeyuan Dong
Summary: Small molecules with natural channel-like functions have potential in treating human diseases. Aromatic helical scaffolds were used to develop foldamer-based ion channels of varying sizes, demonstrating the importance of channel size in ion transport selectivity and leading to the discovery of promising artificial K+ and sodiumpreferential channels.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Jeffrey N. Schellinger, Qifei Sun, John M. Pleinis, Sung-Wan An, Jianrui Hu, Gaelle Mercenne, Iris Titos, Chou-Long Huang, Adrian Rothenfluh, Aylin R. Rodan
Summary: The intracellular chloride concentration in the small ventral lateral (sLN(v)) pacemaker neurons of fruit flies can regulate the length of the circadian period by influencing the activation of the WNK-Fray signaling pathway and the activation of an inwardly rectifying potassium channel. This finding helps us understand the regulatory mechanism of circadian rhythms.
Article
Cell Biology
Antonio Michelucci, Luigi Sforna, Angela Di Battista, Fabio Franciolini, Luigi Catacuzzeno
Summary: Glioblastoma (GBM) is a deadly brain tumor that invades healthy brain tissue through cell migration and invasion. The precise nature of the K+ channels involved in cell volume regulation in this type of tumor has remained uncertain. This study found that hypotonic-induced cell swelling in GBM U87-MG cells triggers the opening of calcium-activated K+ channels, particularly BKCa and IKCa, which play a key role in the regulatory volume decrease following hypotonic shock.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Article
Endocrinology & Metabolism
Bilal Singh, Firas Khattab, Patrick Gilon
Summary: The study reveals that glucose controls alpha-cell [Ca2+](c) and glucagon secretion through multiple mechanisms. Increasing glucose concentration modestly decreases [Ca2+](c) in alpha-cells independently of their K-ATP channels and partly via somatostatin (SST). The changes in [Ca2+](c) parallel changes in glucagon release. Glucose also attenuates the efficacy of Ca2+ on exocytosis.
MOLECULAR METABOLISM
(2022)
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.
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
Physiology
Valeriy Lukyanenko, Joaquin Muriel, Daniel Garman, Leonid Breydo, Robert J. Bloch
Summary: Dysferlin-null myofibers generate abnormal Ca2+ transients, which can be suppressed by a permeable Ca2+ chelator, BAPTA-AM. Dysferlin's C2A domain protects muscle against injury by binding Ca2+ and suppressing abnormal Ca2+ signaling.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Pi-Cheng Cheng, Ruo-Ciao Cheng, Rong-Chi Huang
Summary: Glutamate induces Ca2+ signaling in the suprachiasmatic nucleus (SCN) by activating intracellular mechanisms involving Na+ loads, Na+/K+-ATPase (NKA), and Na+/Ca2+-exchanger (NCX). The presence of Na+ loads leads to slower Ca2+ clearance and increased rebound Ca2+ suppression. However, even in the absence of external Na+, additional Ca2+ handlers are involved in the slower Ca2+ clearance induced by glutamate.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Noemi Toth, Xiao-Hua Zhang, Alexandra Zamaro, Martin Morad
Summary: Mutations in the S4938F-RyR2 gene have been found to cause abnormal Ca2+ signaling and arrhythmia in cardiomyocytes, which may lead to sudden cardiac death or heart failure. The mutations result in smaller L-type Ca2+ currents and activated Ca2+ transients, despite larger caffeine-triggered Ca2+ release signals. This study suggests that the mutations compromise the normal function of Ca2+ release channels and increase the risk of arrhythmia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Melody Li, Mohamed Eltabbal, Hoang- Dai Tran, Bernd Kuhn
Summary: In this study, researchers generated a mouse model of Scn2a insufficiency and found that spontaneous Ca2+ transients in somatosensory cortical neurons, as well as their pairwise co-activities, were decreased in Scn2a ASO mice during spontaneous awake state and induced seizure state. This reduction may be a mechanism driving SCN2A PTV pathology.
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)