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https://www.readbyqxmd.com/read/29150838/gi-530159-a-novel-selective-mechano-sensitive-k2p-channel-opener-reduces-rat-dorsal-root-ganglion-drg-neuron-excitability
#1
Alexandre J C Loucif, Pierre-Philippe Saintot, Jia Liu, Brett M Antonio, Shannon G Zellmer, Katrina Yoger, Emma L Veale, Anna Wilbrey, Kiyoyuki Omoto, Lishuang Cao, Alex Gutteridge, Neil A Castle, Edward B Stevens, Alistair Mathie
BACKGROUND AND PURPOSE: TREK two pore domain potassium channels play a critical role in regulating the excitability of somatosensory nociceptive neurons and are important mediators of pain perception. An understanding of the roles of TREK channels in pain perception and, indeed, in other pathophysiological conditions, has been severely hampered by the lack of potent and/or selective activators and inhibitors. In this study we describe a new, selective opener of TREK channels, GI-530159 (4,4'-(Hexafluoroisopropylidene)bis(p-phenyleneoxy)dianiline)...
November 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29146456/is-more-always-better-how-different-doses-of-exercise-after-incomplete-spinal-cord-injury-affects-the-membrane-properties-of-deep-dorsal-horn-interneurons
#2
M M Rank, M P Galea, R Callister, R J Callister
Interneurons in the deep dorsal horn (DDH) of the spinal cord process somatosensory input, and form an important link between upper and lower motoneurons to subsequently shape motor output. Exercise training after SCI is known to improve functional motor recovery, but little is known about the mechanisms within spinal cord neurons that underlie these improvements. Here we investigate how the properties of DDH interneurons are affected by spinal cord injury (SCI) alone, and SCI in combination with different 'doses' of treadmill exercise training (3, 6, and 9wks)...
November 13, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29146210/novel-intracellular-transport-refractory-mutations-in-kcnh2-identified-in-patients-with-symptomatic-long-qt-syndrome
#3
Daisuke Fukumoto, Wei-Guang Ding, Yuko Wada, Yusuke Fujii, Mari Ichikawa, Koichiro Takayama, Megumi Fukuyama, Koichi Kato, Hideki Itoh, Takeru Makiyama, Mariko Omatsu-Kanbe, Hiroshi Matsuura, Minoru Horie, Seiko Ohno
BACKGROUND: Missense mutations in KCNH2, a gene encoding the Kv11.1 channel, cause long QT syndrome (LQTS) type 2 primarily by disrupting the intracellular transport of Kv11.1 to the plasma membrane. The present study aimed to clarify the functional changes by two novel KCNH2 missense mutations. METHODS: We performed genetic screening of three unrelated symptomatic LQTS probands with family histories of cardiac symptoms. Chinese hamster ovary cells were transfected with wild-type (WT) and/or mutant KCNH2 plasmid and examined by patch-clamp technique...
November 13, 2017: Journal of Cardiology
https://www.readbyqxmd.com/read/29143966/drug-interaction-at-herg-channel-in-vitro-assessment-of-the-electrophysiological-consequences-of-drug-combinations-and-comparison-against-theoretical-models
#4
Barbara Wiśniowska, Bartosz Lisowski, Magdalena Kulig, Sebastian Polak
Drugs carry a proarrhythmic risk, which gets even greater when they are used in combination. In vitro assessment of the proarrhythmic potential of drugs is limited to one compound and thus neglects the potential of drug-drug interactions, including those involving active metabolites. Here we present the results of an in vitro study of potential drug-drug interactions at the level of the hERG channel for the combination of up to three compounds: loratadine, desloratadine and ketoconazole. Experiments were performed at room temperature on an automated patch-clamp device CytoPatch 2, with the use of heterogeneously, stably transfected HEK cells...
November 16, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29143330/short-term-high-fat-diet-primes-excitatory-synapses-for-long-term-depression-in-orexin-neurons
#5
Victoria Linehan, Lisa Fang, Michiru Hirasawa
Overconsumption of high-fat diets is one of the strongest contributing factors to the rise of obesity rates. Orexin neurons are known to be activated by palatable high-fat diet and mediate the activation of the mesolimbic reward pathway, resulting in further food intake. While short-term exposure to high-fat diet is known to induce synaptic plasticity within the mesolimbic pathway, it is unknown if such changes occur in orexin neurons. To investigate this, 3-week old male rats were fed a palatable high-fat western diet (WD) or control chow for 1 week and then in vitro patch clamp recording was performed...
November 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29142093/developmental-changes-in-spinal-neuronal-properties-motor-network-configuration-and-neuromodulation-at-free-swimming-stages-of-xenopus-frog-tadpoles
#6
Stephen Paul Currie, Keith Thomas Sillar
We describe a novel preparation of the isolated brainstem and spinal cord from pro-metamorphic tadpole stages of the South African clawed frog (Xenopus laevis) that permits whole cell patch-clamp recordings from neurons in the ventral spinal cord. Previous research on earlier stages of the same species has provided one of the most detailed understandings of the design and operation of a CPG circuit. Here we have addressed how development sculpts complexity from this more basic circuit. The preparation generates bouts of fictive swimming activity either spontaneously or in response to electrical stimulation of the optic tectum, allowing an investigation into how the neuronal properties, activity patterns and neuromodulation of locomotor rhythm generation change during development...
November 15, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29141003/trpa1-and-trpv1-are-required-for-lidocaine-evoked-calcium-influx-and-neuropeptide-release-but-not-cytotoxicity-in-mouse-sensory-neurons
#7
Mirjam Eberhardt, Thomas Stueber, Jeanne de la Roche, Christine Herzog, Andreas Leffler, Peter W Reeh, Katrin Kistner
BACKGROUND: Local anaesthetics (LA) reduce neuronal excitability by inhibiting voltage-gated Na+ channels. When applied at high concentrations in the direct vicinity of nerves, LAs can also induce relevant irritation and neurotoxicity via mechanisms involving an increase of intracellular Ca2+. In the present study we explored the role of the Ca2+-permeable ion channels TRPA1 and TRPV1 for lidocaine-induced Ca2+-influx, neuropeptide release and neurotoxicity in mouse sensory neurons. METHODS: Cultured dorsal root ganglion (DRG) neurons from wildtype and mutant mice lacking TRPV1, TRPA1 or both channels were explored by means of calcium imaging, whole-cell patch clamp recordings and trypan blue staining for cell death...
2017: PloS One
https://www.readbyqxmd.com/read/29139549/elevated-potassium-outward-currents-in-hyperoxia-treated-atrial-cardiomyocytes
#8
Z Vysotskaya, B Chidipi, J L Rodgers, X Tang, E Samal, N Kolliputi, S Mohapatra, E S Bennett, S K Panguluri
Supplementation of 100% oxygen is a very common intervention in intensive care units (ICU) and critical care centers for patients with dysfunctional lung and lung disorders. Although there is advantage in delivering sufficient levels of oxygen, hyperoxia is reported to be directly associated with increasing in-hospital deaths. Our previous studies reported ventricular and electrical remodeling in hyperoxia treated mouse hearts, and in this article, for the first time, we are investigating the effects of hyperoxia on atrial electrophysiology using whole-cell patch-clamp electrophysiology experiments along with assessment of Kv1...
November 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29138107/effect-of-low-frequency-electrical-stimulation-on-the-high-k-induced-neuronal-hyperexcitability-in-rat-hippocampal-slices
#9
Zahra Ghasemi, Nima Naderi, Amir Shojaei, Mohammad Reza Raoufy, Nooshin Ahmadirad, Javad Mirnajafi-Zadeh
Low frequency electrical stimulation (LFS) is a potential therapeutic method for epilepsy treatment. However, the effect of different LFS characteristics including the number of pulses, intensity and the time of application on its antiepileptic action has not been completely determined. In the present study, epileptiform activity (EA) was induced in hippocampal slices by high-K(+) solution which washed out after 20 min. The changes in the electrophysiological properties of CA1 pyramidal neurons were measured during and 30 min after EA using whole cell patch clamp recording...
November 11, 2017: Neuroscience
https://www.readbyqxmd.com/read/29135436/defective-synaptic-transmission-causes-disease-signs-in-a-mouse-model-of-juvenile-neuronal-ceroid-lipofuscinosis
#10
Benedikt Grünewald, Maren D Lange, Christian Werner, Aet O'Leary, Andreas Weishaupt, Sandy Popp, David A Pearce, Heinz Wiendl, Andreas Reif, Hans C Pape, Klaus V Toyka, Claudia Sommer, Christian Geis
Juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease) caused by mutations in the CLN3 gene is the most prevalent inherited neurodegenerative disease in childhood resulting in widespread central nervous system dysfunction and premature death. The consequences of CLN3 mutation on the progression of the disease, on neuronal transmission, and on central nervous network dysfunction are poorly understood. We used Cln3 knockout (Cln3(Δex7/8)) mice and found increased anxiety-related behavior and impaired aversive learning as well as markedly affected motor function including disordered coordination...
November 14, 2017: ELife
https://www.readbyqxmd.com/read/29134326/inhibition-of-the-voltage-dependent-k-current-by-the-tricyclic-antidepressant-desipramine-in-rabbit-coronary-arterial-smooth-muscle-cells
#11
Sung Eun Shin, Hongliang Li, Jin Ryeol An, Mi Seon Seo, Sung Hun Na, Won-Kyo Jung, Amy L Firth, Kwon-Soo Ha, Eun-Taek Han, Seok-Ho Hong, Il-Whan Choi, Won Sun Park
We describe the effect of a tricyclic antidepressant drug desipramine on voltage-dependent K(+) (Kv) currents in freshly isolated rabbit coronary arterial smooth muscle cells using a conventional whole-cell patch clamp technique. Application of desipramine rapidly decreased the Kv current amplitude in a concentration-dependent manner, with an IC50 value of 5.91 ± 0.18 μM and a Hill coefficient of 0.61 ± 0.09. The steady-state inactivation curves of the Kv channels were not affected by desipramine. However, desipramine shifted the steady-state inactivation curves toward a more negative potential...
November 13, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/29134279/dietary-k-and-cl-independently-regulate-basolateral-conductance-in-principal-and-intercalated-cells-of-the-collecting-duct
#12
Viktor N Tomilin, Oleg Zaika, Arohan R Subramanya, Oleh Pochynyuk
The renal collecting duct contains two distinct cell types, principal and intercalated cells, expressing potassium Kir4.1/5.1 (KCNJ10/16) and chloride ClC-K2 (ClC-Kb in humans) channels on their basolateral membrane, respectively. Both channels are thought to play important roles in controlling systemic water-electrolyte balance and blood pressure. However, little is known about mechanisms regulating activity of Kir4.1/5.1 and ClC-K2/b. Here, we employed patch clamp analysis at the single channel and whole cell levels in freshly isolated mouse collecting ducts to investigate regulation of Kir4...
November 13, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29133341/the-trafficking-protein-ehd2-positively-regulates-cardiac-sarcolemmal-katp-channel-surface-expression-role-in-cardioprotection
#13
Hua Qian Yang, Kundan Jana, Michael J Rindler, William A Coetzee
ATP-sensitive K(+) (KATP) channels uniquely link cellular energy metabolism to membrane excitability and are expressed in diverse cell types that range from the endocrine pancreas to neurons and smooth, skeletal, and cardiac muscle. A decrease in the surface expression of KATP channels has been linked to various disorders, including dysregulated insulin secretion, abnormal blood pressure, and impaired resistance to cardiac injury. In contrast, up-regulation of KATP channel surface expression may be protective, for example, by mediating the beneficial effect of ischemic preconditioning...
November 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29133173/effects-of-norquetiapine-the-active-metabolite-of-quetiapine-on-cloned-herg-potassium-channels
#14
Hong Joon Lee, Jin-Sung Choi, Bok Hee Choi, Sang June Hahn
Quetiapine is an atypical antipsychotic drug that is widely used for the treatment of schizophrenia. It is mainly metabolized by a cytochrome P450 system in the liver. Norquetiapine is a major active metabolite in humans with a pharmacological profile that differs distinctly from that of quetiapine. We used the whole-cell patch-clamp technique to investigate the effects of norquetiapine on hERG channels that are stably expressed in HEK cells. Quetiapine and norquetiapine inhibited the hERG tail currents at -50mV in a concentration-dependent manner with IC50 values of 8...
November 11, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29131433/suppressive-effects-of-morphine-injected-into-the-ventral-bed-nucleus-of-the-stria-terminalis-on-the-affective-but-not-sensory-component-of-pain-in-rats
#15
Chikashi Maruyama, Satoshi Deyama, Yusuke Nagano, Soichiro Ide, Katsuyuki Kaneda, Mitsuhiro Yoshioka, Masabumi Minami
Pain is a complex experience with both sensory and affective components. Clinical and preclinical studies have shown that the affective component of pain can be reduced by doses of morphine lower than those necessary to reduce the sensory component. Although the neural mechanisms underlying the effects of morphine on the sensory component of pain have been investigated extensively, those influencing the affective component remain to be elucidated. The bed nucleus of the stria terminalis (BNST) has been implicated in the regulation of various negative emotional states, including aversion, anxiety, and fear...
November 13, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29131336/molecular-function-of-%C3%AE-7-nicotinic-receptors-as-drug-targets
#16
Cecilia Bouzat, Matías Lasala, Beatriz Elizabeth Nielsen, Jeremías Corradi, María Del Carmen Esandi
Nicotinic acetylcholine receptors (nAChR) are pentameric ligand-gated ion channels involved in many physiological and pathological processes. In vertebrates, there are seventeen different nAChR subunits that combine to yield a variety of receptors with different pharmacology, function, and localization. The homomeric α7 receptor is one of the most abundant nAChRs in the nervous system and it is also present in non-neuronal cells. It plays important roles in cognition, memory, pain, neuroprotection, and inflammation...
November 13, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29131061/kinetic-aspects-of-verapamil-binding-on-rate-on-wild-type-and-six-hkv1-3-mutant-channels
#17
Ann-Kathrin Diesch, Stephan Grissmer
BACKGROUND/AIMS: The human-voltage gated Kv1.3 channel (hKv1.3) is expressed in T- and B lymphocytes. Verapamil is able to block hKv1.3 channels. We characterized the effect of verapamil on currents through hKv1.3 channels paying special attention to the on-rate (kon) of verapamil. By comparing on-rates obtained in wild-type (wt) and mutant channels a binding pocket for verapamil and impacts of different amino acid residues should be investigated. METHODS: Using the whole-cell patch clamp technique the action of verapamil on currents through wild-type and six hKv1...
November 6, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29131007/proteinase-activated-receptor-2-sensitivity-of-amplified-trpa1-activity-in-skeletal-muscle-afferent-nerves-and-exercise-pressor-reflex-in-rats-with-femoral-artery-occlusion
#18
Jihong Xing, Jianhua Li
BACKGROUND/AIMS: Limb ischemia occurs in peripheral artery disease (PAD). Sympathetic nerve activity (SNA) that regulates blood flow directed to the ischemic limb is exaggerated during exercise in this disease, and transient receptor potential channel A1 (TRPA1) in thin-fiber muscle afferents contributes to the amplified sympathetic response. The purpose of the present study was to determine the role of proteinase-activated receptor-2 (PAR2) in regulating abnormal TRPA1 function and the TRPA1-mediated sympathetic component of the exercise pressor reflex...
November 6, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29130489/angiotensin-1-7-modulates-electrophysiological-characteristics-and-calcium-homeostasis-in-pulmonary-veins-cardiomyocytes-via-mas-pi3k-enos-signaling-pathway
#19
Yen-Yu Lu, Wen-Shiann Wu, Yung-Kuo Lin, Chen-Chuan Cheng, Yao-Chang Chen, Shih-Ann Chen, Yi-Jen Chen
BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia, and pulmonary veins (PVs) play a critical role in triggering AF. Angiotensin (Ang)-(1-7) regulates calcium (Ca(2+) ) homeostasis and also plays a critical role in cardiovascular pathophysiology. However, the role of Ang-(1-7) in PV arrhythmogenesis remains unclear. MATERIALS AND METHODS: Conventional microelectrodes, whole-cell patch-clamp, and the Fluo-3 fluorimetric ratio technique were used to record ionic currents and intracellular Ca(2+) in isolated rabbit PV preparations, and in single isolated PV cardiomyocytes, before and after administration of Ang-(1-7)...
November 12, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29129696/the-making-of-a-mushroom-mitosis-nuclear-migration-and-the-actin-network
#20
Elke-Martina Jung, Erika Kothe, Marjatta Raudaskoski
Basidiomycetes feature a prolonged dikaryotic life stage. A dispute over open versus closed mitosis could be solved using in vivo fluorescence videomicroscopy of histone 2B::EGFP and Lifeact labeled Schizophyllum commune. It revealed nuclei to condense to approximately one fifth in diameter during mitotic prophase. In addition, the specifics of clamp cell formation typical of many basidiomycetes included an actin network at the future site of nuclear division, which allowed for cessation of nuclear movement and re-localization of one nucleus towards the emerging clamp cell, while the other divided along the hyphal axis...
November 9, 2017: Fungal Genetics and Biology: FG & B
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