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JOURNAL ARTICLE
Tongtong Zhang, Xincheng Liao, Yuzhi Chen, Xinru Shu, Deshan Liu, Yusheng Yao
PURPOSE: Intravenous regional anesthesia (IVRA) using lidocaine provides effective localized analgesia but its duration is limited. The mechanism by which dexmedetomidine enhances lidocaine IVRA is unclear but may involve modulation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. MATERIALS AND METHODS: Lidocaine IVRA with varying dexmedetomidine concentrations was performed in the tails of Sprague-Dawley rats. Tail-flick and tail-clamping tests assessed IVRA analgesia and anesthesia efficacy and duration...
2024: Drug Design, Development and Therapy
#2
JOURNAL ARTICLE
Mariana Reis Guedes, Sylvana Izaura Salyba Rendeiro de Noronha, Máira Tereza Talma Chírico, Gabriela Dias Carvalho da Costa, Thalles de Freitas Castro, Rory Cristiane Fortes de Brito, Lucas Gabriel Vieira, Thayane Oliveira Reis, Marcelo Carlos Ribeiro, Alexandre Barbosa Reis, Cláudia Martins Carneiro, Frank Silva Bezerra, Nicola Montano, Valdo José Dias da Silva, Rodrigo Cunha de Menezes, Deoclécio Alves Chianca-Jr, Fernanda Cacilda Silva
UNLABELLED: Malnutrition results in autonomic imbalance and heart hypertrophy. Overexpression of hyperpolarization-activated cyclic nucleotide-gated channels (HCN) in the left ventricles (LV) is linked to hypertrophied hearts and abnormal myocardium automaticity. Given that ivabradine (IVA) has emerging pleiotropic effects, in addition to the widely known bradycardic response, this study evaluated if IVA treatment could repair the autonomic control and cardiac damages in malnourished rats...
April 11, 2024: Life Sciences
#3
JOURNAL ARTICLE
Xingyou Huang, Seok Choi, Wenhao Wu, Pawan Kumar Shahi, Jun Hyung Lee, Chansik Hong, Jae Yeoul Jun
We examined the localization of the 5-hydroxytryptamine (5-HT) receptor and its effects on mouse colonic interstitial cells of Cajal (ICCs) using electrophysiological techniques. Treatment with 5-HT increased the pacemaker activity in colonic ICCs with depolarization of membrane potentials in a dose-dependent manner. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blockers blocked pacemaker activity and 5-HT-induced effects. Moreover, an adenylate cyclase inhibitor inhibited 5-HT-induced effects, and cell-permeable 8-bromo-cAMP increased the pacemaker activity...
April 3, 2024: International Journal of Molecular Sciences
#4
JOURNAL ARTICLE
Polina Lyuboslavsky, Gregory J Ordemann, Alena Kizimenko, Audrey C Brumback
At the heart of the prefrontal network is the mediodorsal thalamus (MD). Despite the importance of MD in a broad range of behaviors and neuropsychiatric disorders, little is known about the physiology of neurons in MD. We injected the retrograde tracer cholera toxin subunit B (CTB) into the medial prefrontal cortex (mPFC) of adult wildtype mice. We prepared acute brain slices and used current clamp electrophysiology to measure and compare the intrinsic properties of the neurons in MD that project to mPFC (MD→mPFC neurons)...
April 3, 2024: Journal of Neurophysiology
#5
JOURNAL ARTICLE
Fusun Doldur-Balli, Sandra P Smieszek, Brendan T Keenan, Amber J Zimmerman, Olivia J Veatch, Christos M Polymeropoulos, Gunther Birznieks, Mihael H Polymeropoulos
Hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels generate electrical rhythmicity in various tissues although primarily heart, retina and brain. The HCN channel blocker compound, Ivabradine (Corlanor), is approved by the US Food and Drug Administration (FDA) as a medication to lower heart rate by blocking hyperpolarization activated inward current in the sinoatrial node. In addition, a growing body of evidence suggests a role for HCN channels in regulation of sleep/wake behavior. Zebrafish larvae are ideal model organisms for high throughput drug screening, drug repurposing and behavioral phenotyping studies...
2024: Frontiers in Neuroscience
#6
REVIEW
Daniel Kim, Hyeonhee Roh, Hyung-Min Lee, Sang Jeong Kim, Maesoon Im
Transmembrane proteins known as hyperpolarization-activated cyclic nucleotide-gated (HCN) channels control the movement of Na+ and K+ ions across cellular membranes. HCN channels are known to be involved in crucial physiological functions in regulating neuronal excitability and rhythmicity, and pacemaker activity in the heart. Although HCN channels have been relatively well investigated in the brain, their distribution and function in the retina have received less attention, remaining their physiological roles to be comprehensively understood...
2024: Frontiers in Neuroanatomy
#7
Clara Houdayer, A Marie Phillips, Marie Chabbert, Jennifer Bourreau, Reza Maroofian, Henry Houlden, Kay Richards, Nebal Waill Saadi, Eliška Dad'ová, Patrick Van Bogaert, Mailys Rupin, Boris Keren, Perrine Charles, Thomas Smol, Audrey Riquet, Lynn Pais, Anne O'Donnell-Luria, Grace E VanNoy, Allan Bayat, Rikke S Møller, Kern Olofsson, Rami Abou Jamra, Steffen Syrbe, Majed Dasouki, Laurie H Seaver, Jennifer A Sullivan, Vandana Shashi, Fowzan S Alkuraya, Alexis F Poss, J Edward Spence, Rhonda E Schnur, Ian C Forster, Chaseley E Mckenzie, Cas Simons, Min Wang, Penny Snell, Kavitha Kothur, Michael Buckley, Tony Roscioli, Noha Elserafy, Benjamin Dauriat, Vincent Procaccio, Daniel Henrion, Guy Lenaers, Estelle Colin, Nienke E Verbeek, Koen L Van Gassen, Claire Legendre, Dominique Bonneau, Christopher A Reid, Katherine B Howell, Alban Ziegler, Christian Legros
Hyperpolarization activated Cyclic Nucleotide (HCN) gated channels are crucial for various neurophysiological functions, including learning and sensory functions, and their dysfunction are responsible for brain disorders, such as epilepsy. To date, HCN2 variants have only been associated with mild epilepsy and recently, one monoallelic missense variant has been linked to developmental and epileptic encephalopathy. Here, we expand the phenotypic spectrum of HCN2- related disorders by describing twenty-one additional individuals from fifteen unrelated families carrying HCN2 variants...
March 22, 2024: medRxiv
#8
JOURNAL ARTICLE
Matteo Martin, Morten Gram Pedersen
Cyclic AMP controls neuronal ion channel activity. For example hyperpolarization-activated cyclic nucleotide-gated (HCN) and M-type K+ channels are activated by cAMP. These effects have been suggested to be involved in astrocyte control of neuronal activity, for example, by controlling the action potential firing frequency. In cortical neurons, cAMP can induce mixed-mode oscillations (MMOs) consisting of small-amplitude, subthreshold oscillations separating complete action potentials, which lowers the firing frequency greatly...
March 22, 2024: PLoS Computational Biology
#9
REVIEW
Zeng-Xin Qi, Qi Yan, Xiu-Juan Fan, Jian-Ya Peng, Hui-Xian Zhu, Yi-Miao Jiang, Liang Chen, Qian-Xing Zhuang
Parkinson's disease (PD) is a motor disorder resulting from dopaminergic neuron degeneration in the substantia nigra caused by age, genetics, and environment. The disease severely impacts a patient's quality of life and can even be life-threatening. The hyperpolarization-activated cyclic nucleotide-gated (HCN) channel is a member of the HCN1-4 gene family and is widely expressed in basal ganglia nuclei. The hyperpolarization-activated current mediated by the HCN channel has a distinct impact on neuronal excitability and rhythmic activity associated with PD pathogenesis, as it affects the firing activity, including both firing rate and firing pattern, of neurons in the basal ganglia nuclei...
March 13, 2024: Cellular and Molecular Life Sciences: CMLS
#10
JOURNAL ARTICLE
Paul G Morris, Joseph D Taylor, Julian F R Paton, Alain Nogaret
The dysfunction of ion channels is a causative factor in a variety of neurological diseases, thereby defining the implicated channels as key drug targets. The detection of functional changes in multiple specific ionic currents currently presents a challenge, particularly when the neurological causes are either a priori unknown, or are unexpected. Traditional patch clamp electrophysiology is a powerful tool in this regard but is low throughput. Here, we introduce a single-shot method for detecting alterations amongst a range of ion channel types from subtle changes in membrane voltage in response to a short chaotically driven current clamp protocol...
March 12, 2024: Scientific Reports
#11
JOURNAL ARTICLE
Kyle A Lyman, Ye Han, Andrew P Robinson, Samuel E Weinberg, Daniel W Fisher, Robert J Heuermann, Reagan E Lyman, Dong Kyu Kim, Andreas Ludwig, Navdeep S Chandel, Mark D Does, Stephen D Miller, Dane M Chetkovich
Mature oligodendrocytes (OLG) are the myelin-forming cells of the central nervous system. Recent work has shown a dynamic role for these cells in the plasticity of neural circuits, leading to a renewed interest in voltage-sensitive currents in OLG. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and their respective current (I h ) were recently identified in mature OLG and shown to play a role in regulating myelin length. Here we provide a biochemical and electrophysiological characterization of HCN channels in cells of the oligodendrocyte lineage...
2024: Frontiers in Cellular Neuroscience
#12
JOURNAL ARTICLE
Masashi Watanave, Mika Kawachi, Ayumu Konno, Ryo Aoki, Yuuki Fukai, Yasunori Matsuzaki, Ryosuke Kaneko, Hirokazu Hirai
Protein kinase C γ (PKCγ), a neuronal isoform present exclusively in the central nervous system, is most abundantly expressed in cerebellar Purkinje cells (PCs). Targeted deletion of PKCγ causes a climbing fiber synapse elimination in developing PCs and motor deficit. However, physiological roles of PKCγ in adult mouse PCs are little understood. In this study, we aimed to unravel the roles of PKCγ in mature mouse PCs by deleting PKCγ from adult mouse PCs of PKCγ fl/fl mice via cerebellar injection of adeno-associated virus (AAV) vectors expressing Cre recombinase under the control of the PC-specific L7-6 promoter...
2024: Frontiers in Cellular Neuroscience
#13
JOURNAL ARTICLE
Bhupesh Vaidya, Dibya S Padhy, Hem C Joshi, Shyam S Sharma, Jitendra Narain Singh
Parkinson's disease (PD) is a neurodegenerative condition linked to the deterioration of motor and cognitive performance. It produces degeneration of the dopaminergic neurons along the nigrostriatal pathway in the central nervous system (CNS), which leads to symptoms such as bradykinesias, tremors, rigidity, and postural instability. There are several medications currently approved for the therapy of PD, but a permanent cure for it remains elusive. With the aging population set to increase, a number of PD cases are expected to shoot up in the coming times...
2024: Methods in Molecular Biology
#14
JOURNAL ARTICLE
Ji-Jie Pang, Xiaolong Jiang, Samuel M Wu
Photoreceptors are electrically coupled to one another, and the spatiotemporal properties of electrical synapses in a two-dimensional retinal network are still not well-studied, because of the limitation of the single electrode or pair recording techniques which do not allow simultaneously measuring responses of multiple photoreceptors at various locations in the retina. A multiple electrode recording system is needed. In this study we investigate the network properties of the two-dimensional rod coupled array of the salamander retina (both sexes were used) by using the newly available multiple patch electrode system that allows simultaneous recordings from up to 8 cells, and to determine the electrical connectivity among multiple rods...
February 29, 2024: Journal of Neuroscience
#15
JOURNAL ARTICLE
Nelson A Rodríguez, Nihir Patel, Rafael Dariolli, Simon Ng, Angelika G Aleman, Jingqi Q X Gong, Hung-Mo Lin, Matthew Rodríguez, Rebecca Josowitz, Katia Sol-Church, Karen W Gripp, Xianming Lin, Soomin C Song, Glenn I Fishman, Eric A Sobie, Bruce D Gelb
BACKGROUND: Germline HRAS gain-of-function pathogenic variants cause Costello syndrome (CS). During early childhood, 50% of patients develop multifocal atrial tachycardia, a treatment-resistant tachyarrhythmia of unknown pathogenesis. This study investigated how overactive HRAS activity triggers arrhythmogenesis in atrial-like cardiomyocytes (ACMs) derived from human-induced pluripotent stem cells bearing CS-associated HRAS variants. METHODS: HRAS Gly12 mutations were introduced into a human-induced pluripotent stem cells-ACM reporter line...
February 28, 2024: Circulation. Arrhythmia and Electrophysiology
#16
JOURNAL ARTICLE
Lena H Nguyen, Youfen Xu, Maanasi Nair, Angelique Bordey
Brain somatic mutations in various components of the mTOR complex 1 (mTORC1) pathway have emerged as major causes of focal malformations of cortical development and intractable epilepsy. While these distinct gene mutations converge on excessive mTORC1 signaling and lead to common clinical manifestations, it remains unclear whether they cause similar cellular and synaptic disruptions underlying cortical network hyperexcitability. Here, we show that in utero activation of the mTORC1 activator genes, Rheb or MTOR , or biallelic inactivation of the mTORC1 repressor genes, Depdc5 , Tsc1 , or Pten in the mouse medial prefrontal cortex leads to shared alterations in pyramidal neuron morphology, positioning, and membrane excitability but different changes in excitatory synaptic transmission...
February 27, 2024: ELife
#17
JOURNAL ARTICLE
Naohisa Umeya, Yuki Yoshizawa, Kosuke Fukuda, Keigo Ikeda, Mami Kamada, Hiroshi Inada, Toru Usui, Izuru Miyawaki
Ivabradine, a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel inhibitor, has been reported to induce photosensitivity-related visual disturbances such as phosphene in humans. Ivabradine-induced visual disturbances are caused by inhibition of HCN channels in the retina, and the mechanisms have been verified using HCN channel knockout mice and electroretinography (ERG). However, in rats, classical ERG using single flash light stimulus with standard analyses of waveform amplitude and latency has not revealed abnormal retinal function after administration of ivabradine...
February 22, 2024: Experimental Eye Research
#18
JOURNAL ARTICLE
Stefan Kuschke, Susanne Thon, Christian Sattler, Tina Schwabe, Klaus Benndorf, Ralf Schmauder
The cooperative action of the subunits in oligomeric receptors enables fine-tuning of receptor activation, as demonstrated for the regulation of voltage-activated HCN pacemaker ion channels by relating cAMP binding to channel activation in ensemble signals. HCN channels generate electric rhythmicity in specialized brain neurons and cardiomyocytes. There is conflicting evidence on whether binding cooperativity does exist independent of channel activation or not, as recently reported for detergent-solubilized receptors positioned in zero-mode waveguides...
February 27, 2024: Proceedings of the National Academy of Sciences of the United States of America
#19
JOURNAL ARTICLE
Xiaona Wang, Qian Wang, Min Song, Yihui Wang, Xianzhi Shen, Yanyun Sun, Chun Guo, Panpan Geng, Chaolin Ma, Xinchun Jin
BACKGROUND: Systemic inflammation in which lipopolysaccharide (LPS) is released into circulation can cause cognitive dysfunction and we have previously shown that LPS impaired working memory (WM) which refers to the ability to guide incoming behavior by retrieving recently acquired information. However, the mechanism is not very clear, and currently, there is no approved strategy to improve inflammation-induced WM deficit. Notably, epidemiological studies have demonstrated a lower occurrence rate of inflammatory-related diseases in smoking patients, suggesting that inflammation-induced WM impairment may be improved by nicotine treatment...
February 2024: CNS Neuroscience & Therapeutics
#20
JOURNAL ARTICLE
Satchithananthi Aruljothi, Rohit Manchanda
The urothelium is the innermost layer of the bladder wall; it plays a pivotal role in bladder sensory transduction by responding to chemical and mechanical stimuli. The urothelium also acts as a physical barrier between urine and the outer layers of the bladder wall. There is intricate sensory communication between the layers of the bladder wall and the neurons that supply the bladder, which eventually translates into the regulation of mechanical activity. In response to natural stimuli, urothelial cells release substances such as ATP, nitric oxide (NO), substance P, acetylcholine (ACh), and adenosine...
February 12, 2024: Journal of Computational Neuroscience
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