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Potassium Channels

Péter Hertelendy, Dániel P Varga, Ákos Menyhárt, Ferenc Bari, Eszter Farkas
Secondary injury following acute brain insults significantly contributes to poorer neurological outcome. The spontaneous, recurrent occurrence of spreading depolarization events (SD) has been recognized as a potent secondary injury mechanism in subarachnoid hemorrhage, malignant ischemic stroke and traumatic brain injury. In addition, SD is the underlying mechanism of the aura symptoms of migraineurs. The susceptibility of the nervous tissue to SD is subject to the metabolic status of the tissue, the ionic composition of the extracellular space, and the functional status of ion pumps, voltage-gated and other cation channels, glutamate receptors and excitatory amino acid transporters...
October 15, 2018: Neurochemistry International
Xianmin Kong, Shanshan Tian, Tao Chen, Yinghui Huang
The design of pattern that limit the hippocampal cells growth is an important explore for realizing a simplified artificial neuronal network in vitro. In this study, we examined the pattern in micro-fluidic chip to stipulate the hippocampal cells adhesion, growth and the formation of a functional neuronal network in vitro. Patch clamp recording technique was used to detect the growth situation and biological function of the haippocampal cells on the micro-fluidic chip which could simulate environment in vivo...
October 18, 2018: International Journal of Neuroscience
Juan J Ferreira, Alice Butler, Richard Stewart, Ana Laura Gonzalez-Cota, Pascale Lybaert, Chinwendu Amazu, Erin L Reinl, Monali Wakle-Prabagaran, Lawrence Salkoff, Sarah K England, Celia M Santi
KEY POINTS: At the end of pregnancy, the uterus transitions from a quiescent state to a highly contractile state. This transition requires that the uterine (myometrial) smooth muscle cells increase their excitability, but how this occurs is not fully understood. We identified SLO2.1, a potassium channel heretofore unknown to be in uterine smooth muscle as a potential significant contributor to the electrical excitability of myometrial smooth muscle cells. We found that activity of the SLO2...
October 17, 2018: Journal of Physiology
Saba Munawar, Monique J Windley, Edwin G Tse, Matthew H Todd, Adam P Hill, Jamie I Vandenberg, Ishrat Jabeen
The hERG (human ether-a-go-go-related gene) encoded potassium ion (K+ ) channel plays a major role in cardiac repolarization. Drug-induced blockade of hERG has been a major cause of potentially lethal ventricular tachycardia termed Torsades de Pointes (TdPs). Therefore, we presented a pharmacoinformatics strategy using combined ligand and structure based models for the prediction of hERG inhibition potential (IC50 ) of new chemical entities (NCEs) during early stages of drug design and development. Integrated GRid-INdependent Descriptor (GRIND) models, and lipophilic efficiency (LipE), ligand efficiency (LE) guided template selection for the structure based pharmacophore models have been used for virtual screening and subsequent hERG activity (pIC50 ) prediction of identified hits...
2018: Frontiers in Pharmacology
Sebastian Beck, Jing Yu-Strzelczyk, Dennis Pauls, Oana M Constantin, Christine E Gee, Nadine Ehmann, Robert J Kittel, Georg Nagel, Shiqiang Gao
Optogenetic manipulation of cells or living organisms became widely used in neuroscience following the introduction of the light-gated ion channel channelrhodopsin-2 (ChR2). ChR2 is a non-selective cation channel, ideally suited to depolarize and evoke action potentials in neurons. However, its calcium (Ca2+ ) permeability and single channel conductance are low and for some applications longer-lasting increases in intracellular Ca2+ might be desirable. Moreover, there is need for an efficient light-gated potassium (K+ ) channel that can rapidly inhibit spiking in targeted neurons...
2018: Frontiers in Neuroscience
Nathalie Nasr, Adèle Faucherre, Marc Borsotto, Catherine Heurteaux, Jean Mazella, Chris Jopling, Hamid Moha Ou Maati
KCNK2 is a 2 pore domain potassium channel involved in maintaining cellular membrane resting potentials. Although KCNK2 is regarded as a mechanosensitive ion channel, it can also be gated chemically. Previous research indicates that KCNK2 expression is particularly enriched in neuronal and cardiac tissues. In this respect, KCNK2 plays an important role in neuroprotection and has also been linked to cardiac arrhythmias. KCNK2 has subsequently become an attractive pharmacologic target for developing preventative/curative strategies for neuro/cardio pathophysiological conditions...
October 17, 2018: Scientific Reports
Colin G Nichols, Sun-Joo Lee
Potassium channels that exhibit the property of inward rectification (Kir channels) are present in most cells. Cloning of the first Kir channel genes 25 years ago led to recognition that inward rectification is a consequence of voltage-dependent block by cytoplasmic polyamines, which are also ubiquitously present in animal cells. Upon cellular depolarization, these polycationic metabolites enter the Kir channel pore from the intracellular side, blocking the movement of K+ ions through the channel. As a consequence, high K+ conductance at rest can provide very stable negative resting potentials, but polyamine-mediated blockade at depolarized potentials ensures, for instance, the long plateau phase of the cardiac action potential, an essential feature for a stable cardiac rhythm...
October 17, 2018: Journal of Biological Chemistry
Chang You, Antonia Savarese, Bertha J Vandegrift, Donghong He, Subhash C Pandey, Amy W Lasek, Mark S Brodie
Alcohol excitation of the ventral tegmental area (VTA) is important in neurobiological processes related to the development of alcoholism. The ionotropic receptors on VTA neurons that mediate ethanol-induced excitation have not been identified. Quinidine blocks ethanol excitation of VTA neurons, and blockade of two-pore potassium channels is among the actions of quinidine. Therefore two-pore potassium channels in the VTA may be potential targets for the action of ethanol. Here, we explored whether ethanol activation of VTA neurons is mediated by the two-pore potassium channel KCNK13...
October 14, 2018: Neuropharmacology
Olufunmilayo O Adeyemi, Ismail O Ishola, Elizabeth T Adesanya, Destiny O Alohan
Background Tetracera alnifolia Willd. (Dilleniaceae) is used in traditional African Medicine for the treatment of headache, abdominal pain, and rheumatism. Hence, this study sought to investigate the antinociceptive and anti-inflammatory effects of the hydroethanolic leaf extract of T. alnifolia (HeTA) in rodents. Methods Antinociceptive activity was evaluated using the acetic acid-induced writhing, formalin-/capsaicin-induced paw licking and hot plate tests in mice. The contribution of opioidergic, l-arginine-nitric oxide, and ATP-sensitive potassium channel pathways in HeTA-induced antinociception was also evaluated...
October 17, 2018: Journal of Basic and Clinical Physiology and Pharmacology
Peter J West, Gerald W Saunders, Peggy Billingsley, Misty D Smith, H Steve White, Cameron S Metcalf, Karen S Wilcox
OBJECTIVE: Approximately 30% of patients with epilepsy are refractory to existing antiseizure drugs (ASDs). Given that the properties of the central nervous systems of these patients are likely to be altered due to their epilepsy, tissues from rodents that have undergone epileptogenesis might provide a therapeutically relevant disease substrate for identifying compounds capable of attenuating pharmacoresistant seizures. To facilitate the development of such a model, this study describes the effects of classical glutamate receptor antagonists and 20 ASDs on recurrent epileptiform discharges (REDs) in brain slices derived from the kainate-induced status epilepticus model of temporal lobe epilepsy (KA-rats)...
October 17, 2018: Epilepsia
Yue Yang, Song Li, Zi-Run Jin, Hong-Bo Jing, Hong-Yan Zhao, Bo-Heng Liu, Ya-Jing Liang, Ling-Yu Liu, Jie Cai, You Wan, Guo-Gang Xing
Cancer-associated pain is debilitating. Understanding the mechanisms that cause it can inform drug development that may improve quality of life in patients. Here, we found that the reduced abundance of potassium channels called TRESK in dorsal root ganglion (DRG) neurons sensitized nociceptive sensory neurons and cancer-associated pain. Overexpressing TRESK in DRG neurons suppressed tumor-induced neuronal hyperexcitability and pain hypersensitivity in bone metastasis model rats, whereas knocking down TRESK increased neuronal hyperexcitability and pain hypersensitivity in normal rats...
October 16, 2018: Science Signaling
Daniel M Sigg, Hsueh-Kai Chang, Ru-Chi Shieh
Potassium-selective inward rectifier (Kir) channels are a class of membrane proteins necessary for maintaining stable resting membrane potentials, controlling excitability, and shaping the final repolarization of action potentials in excitable cells. In addition to the strong inward rectification of the ionic current caused by intracellular blockers, Kir2.1 channels possess "weak" inward rectification observed in inside-out patches after prolonged washout of intracellular blockers. The mechanisms underlying strong inward rectification have been attributed to voltage-dependent block by intracellular Mg2+ and polyamines; however, the mechanism responsible for weak rectification remains elusive...
October 16, 2018: Journal of General Physiology
Mark A Seefeld, Hong Lin, Joerg Holenz, Dave Downie, Brian Donovan, Tingting Fu, Kishore Pasikanti, Wei Zhen, Matthew Cato, Khuram W Chaudhary, Pat Brady, Tania Bakshi, Dwight Morrow, Sridharan Rajagopal, Swapan Kumar Samanta, Naveena Madhyastha, Bharathi Mohan Kuppusamy, Robert W Dougherty, Ravi Bhamidipati, Zainuddin Mohd, Guy A Higgins, Mark Chapman, Céline Rouget, Philippe Lluel, Yasuji Matsuoka
Neuronal voltage-gated potassium channels, KV 7s, are the molecular mediators of the M current and regulate membrane excitability in the central and peripheral neuronal systems. Herein, we report novel small molecule KV 7 openers that demonstrate anti-seizure activities in electroshock and pentylenetetrazol-induced seizure models without influencing Rotarod readouts in mice. The anti-seizure activity was determined to be proportional to the unbound concentration in the brain. KV 7 channels are also expressed in the bladder smooth muscle (detrusor) and activation of these channels may cause localized undesired effects...
September 29, 2018: Bioorganic & Medicinal Chemistry Letters
Punnaka Pongpanich, Pasvich Pitakpaiboonkul, Kullaya Takkavatakarn, Kearkiat Praditpornsilpa, Somchai Eiam-Ong, Paweena Susantitaphong
BACKGROUND: The prevalence of hypertension and its associated complications are markedly growing. Most patients need more than one drug to achieve blood pressure (BP) target. However, most guidelines only focus on the first-line treatment. We conducted a meta-analysis to explore the benefits of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs) combined with calcium channel blockers (CCBs) on metabolic, renal, and cardiovascular outcomes in hypertensive patients...
October 15, 2018: International Urology and Nephrology
Xinyuan Gong, Xikun Han, Xiangfeng Lu, Jing Chen, Jianfeng Huang, Tanika N Kelly, Chung-Shiuan Chen, Jiang He, Dongfeng Gu, Shufeng Chen
Blood pressure (BP) responses to dietary sodium intervention vary among individuals. The inwardly rectifying potassium channel (Kir) is a potassium-selective ion channel that allows potassium ions to move more easily into rather than out of the cell. We aimed to investigate the associations of Kir genes with BP responses to dietary sodium intervention. A 7-day low-sodium intervention followed by a 7-day high-sodium intervention was conducted among 1906 participants. BP measurements were obtained at baseline and during each dietary intervention...
October 15, 2018: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Mubarak Ali, Ishtiaq Ahmed, Saima Nasir, Ivana Duznovic, Christof M Niemeyer, Wolfgang Ensinger
Solid-state nanofluidic pores have been attracting considerable attention of scientific community because of their structural and chemical resemblance with biological ion channels for mimicking biological processes in living systems. Compared to ion channels, synthetic nanopores exhibit high stability, control over pore dimensions (size and geometry) and their surface chemical properties can be tuned on demand. Therefore, they are considered perfect candidates to design and develop nanofluidic sensory devices by introducing a variety of functional moieties on the inner pore surface...
December 18, 2018: Analytica Chimica Acta
Min Li, Jian Wang, Dewu Liu, Heping Huang
Growing evidence suggests that long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) are involved in the occurrence and development of tumors and fibrotic diseases. However, the integrated analysis of lncRNA and circRNA expression, alongside associated co‑expression and competing endogenous RNA (ceRNA) networks, has not yet been performed in human hypertrophic scars (HS). The present study compared the expression levels of lncRNAs, circRNAs and mRNAs in human HS and normal skin tissues by high‑throughput RNA sequencing...
October 15, 2018: Molecular Medicine Reports
Nathanael Matei, Richard Camara, John H Zhang
Clinical and pre-clinical studies have reported a broad range of applications for hydrogen gas therapy. Classically, conventional antioxidant therapy is limited because it neutralizes both the detrimental and protective effects of reactive oxygen species. As a weak reducing agent, hydrogen gas avoids this paradox by reacting with strong oxidants while leaving other beneficial oxidants reactive. This review gathers a promising list of hydrogen gas applications that merit further mechanistic investigation and additional therapeutic trials...
July 2018: Medical Gas Research
Dong Ho Woo, Jin Young Bae, Min-Ho Nam, Heeyoung An, Yeon Ha Ju, Joungha Won, Jae Hyouk Choi, Eun Mi Hwang, Kyung-Seok Han, Yong Chul Bae, C Justin Lee
Recently, μ-opioid receptor (MOR), one of the well-known Gi-protein coupled receptors (Gi-GPCR), was reported to be highly expressed in the hippocampal astrocytes. However, the role of astrocytic MOR has not been investigated. Here we report that activation of astrocytic MOR by [D-Ala2 ,N-MePhe4 ,Gly-ol]-enkephalin (DAMGO), a selective MOR agonist, causes a fast glutamate release using sniffer patch technique. We also found that the DAMGO-induced glutamate release was not observed in the astrocytes from MOR-deficient mice and MOR-short hairpin RNA (shRNA)-expressed astrocytes...
2018: Frontiers in Cellular Neuroscience
Chong-Jin Zhong, Miao-Miao Chen, Ming Lu, Jian-Hua Ding, Ren-Hong Du, Gang Hu
ATP-sensitive potassium (K-ATP) channels, coupling cell metabolism to cell membrane potential, are involved in brain diseases including stroke. Emerging evidence shows that astrocytes play important roles in the pathophysiology of cerebral ischemia. Kir6.1, a pore-forming subunit of K-ATP channel, is prominently expressed in astrocytes and participates in regulating its function. However, the exact role of astrocytic Kir6.1-containg K-ATP channel (Kir6.1/K-ATP) in ischemic stroke remains unclear. Here, we found that astrocytic Kir6...
October 10, 2018: Experimental Neurology
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