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https://www.readbyqxmd.com/read/29333591/differential-inhibition-of-nav1-7-and-neuropathic-pain-by-hybridoma-produced-and-recombinant-monoclonal-antibodies-that-target-nav1-7-differential-activities-of-nav1-7-targeting-monoclonal-antibodies
#1
Sangsu Bang, Jiho Yoo, Xingrui Gong, Di Liu, Qingjian Han, Xin Luo, Wonseok Chang, Gang Chen, Sang-Taek Im, Yong Ho Kim, Judith A Strong, Ma-Zhong Zhang, Jun-Ming Zhang, Seok-Yong Lee, Ru-Rong Ji
The voltage-gated Na+ channel subtype Nav1.7 is important for pain and itch in rodents and humans. We previously showed that a Nav1.7-targeting monoclonal antibody (SVmab) reduces Na+ currents and pain and itch responses in mice. Here, we investigated whether recombinant SVmab (rSVmab) binds to and blocks Nav1.7 similar to SVmab. ELISA tests revealed that SVmab was capable of binding to Nav1.7-expressing HEK293 cells, mouse DRG neurons, human nerve tissue, and the voltage-sensor domain II of Nav1.7. In contrast, rSVmab showed no or weak binding to Nav1...
January 15, 2018: Neuroscience Bulletin
https://www.readbyqxmd.com/read/29330129/estradiol-up-regulates-l-type-ca2-channels-via-membrane-bound-estrogen-receptor-phosphoinositide-3kinase-akt-camp-response-element-binding-protein-signaling-pathway
#2
Xiaoyan Yang, Xiaofang Mao, Gao Xu, Shasha Xing, Ansuman Chattopadhyay, Si Jin, Guy Salama
BACKGROUND: In long QT type-2 (LQT2), women are more prone to lethal arrhythmias called Torsade de Pointes (TdP) than men. We previously reported that 17-β-estradiol (E2) upregulates L-type Ca2+-channels and current (ICa,L) (∼30%) in rabbit ventricular myocytes by a classical genomic-mechanism mediated by estrogen-receptor-α (ER)α. In LQT2 ( IKr-blockade or bradycardia), the higher Ca2+ influx via ICa,L, causes Ca2+-overload, spontaneous sarcoplasmic reticulum Ca2+-release, and re-activation of ICa,L that trigger early afterdepolarizations (EADs) and TdP...
January 9, 2018: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/29319186/the-large-conductance-voltage-and-ca2-activated-k-channel-and-its-%C3%AE-1-subunit-modulate-mouse-uterine-artery-function-during-pregnancy
#3
Ramón A Lorca, Monali Wakle-Prabagaran, William E Freeman, Meghan K Pillai, Sarah K England
Insufficient vasodilation of the uterine artery (UA) during pregnancy leads to poor utero-placental perfusion, contributing to intrauterine growth restriction and fetal loss. Activity of the large conductance Ca2+ -activated K+ (BKCa ) channel increases in the UA during pregnancy, and its inhibition reduces uterine blood flow, highlighting a role of this channel in UA adaptation to pregnancy. The auxiliary γ1-subunit increases BKCa activation in vascular smooth muscle, but its role in pregnancy-associated UA remodelling is unknown...
January 10, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29318456/voltage-dependence-of-the-ca2-transient-in-endocardial-and-epicardial-myocytes-from-the-left-ventricle-of-goto-kakizaki-type-2-diabetic-rats
#4
Lina Al Kury, Vadym Sydorenko, Manal M A Smail, Muhammad Anwar Qureshi, Anatoliy Shmygol, Murat Oz, Jaipaul Singh, Frank Christopher Howarth
Diabetes mellitus is a major global health disorder and, currently, over 450 million people have diabetes with 90% suffering from type 2 diabetes. Left untreated, diabetes may lead to cardiovascular diseases which are a leading cause of death in diabetic patients. Calcium is the trigger and regulator of cardiac muscle contraction and derangement in cellular Ca2+ homeostasis, which can result in heart failure and sudden cardiac death. It is of paramount importance to investigate the regional involvement of Ca2+ in diabetes-induced cardiomyopathy...
January 9, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29313436/down-regulation-of-kv4-3-channels-and-a-type-k-currents-in-v2-trigeminal-ganglion-neurons-of-rats-following-oxaliplatin-treatment
#5
Viacheslav Viatchenko-Karpinski, Jennifer Ling, Jianguo G Gu
Chemotherapy drugs such as oxaliplatin can increase nociceptive neuron excitability to result in neuropathic pain in orofacial and other regions in patients following chemotherapy. However, mechanisms underlying chemotherapy-induced increases of nociceptive neuron excitability are not fully understood. Kv4.3 channels are voltage-gated K+ channels mediating A-type K+ (IA) currents to control neuronal excitability. In the present study, we examined Kv4.3 channel expression on trigeminal neurons that innervate orofacial regions (V2 TG neurons) of rats using immunostaining method...
January 2018: Molecular Pain
https://www.readbyqxmd.com/read/29311484/molecular-determinants-of-%C3%AE-3%C3%AE-4-nicotinic-acetylcholine-receptors-inhibition-by-triterpenoids
#6
Sanung Eom, Yoon Suh Kim, Sung Bae Lee, Shinhwa Noh, Hye Duck Yeom, Hyunsu Bae, Jun-Ho Lee
In a previous work, we reported the regulatory role of the triterpenoids on 5-hydroxytryptamine (5-HT)3A receptors activity in Xenopus laevis oocytes (Eur. J. Pharmacol., 615, 2009, Lee et al.). In the present report, we studied the modulation of triterpenoids on the activity of the human nicotinic acetylcholine receptor type α3β4. Two-electrode voltage clamp experiments were used to test acetylcholine mediated inward current (IACh). Treatment with triterpenoids (dehydroeburicoic acid, 6α-hydroxypolyporenic acid C and pachymic acid) inhibited IACh in a concentration dependent and reversible manner...
2018: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29311162/differential-expression-and-remodeling-of-transient-outward-potassium-currents-in-human-left-ventricles
#7
Eric K Johnson, Steven J Springer, Wei Wang, Edward J Dranoff, Yan Zhang, Evelyn M Kanter, Kathryn A Yamada, Jeanne M Nerbonne
BACKGROUND: Myocardial, transient, outward currents, Ito, have been shown to play pivotal roles in action potential (AP) repolarization and remodeling in animal models. The properties and contribution of Ito to left ventricular (LV) repolarization in the human heart, however, are poorly defined. METHODS AND RESULTS: Whole-cell, voltage-clamp recordings, acquired at physiological (35°C to 37°C) temperatures, from myocytes isolated from the LV of nonfailing human hearts identified 2 distinct transient currents, Ito,fast (Ito,f) and Ito,slow (Ito,s), with significantly (P<0...
January 2018: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/29306054/tyrosine-phosphorylation-determines-afterdischarge-initiation-by-regulating-an-ionotropic-cholinergic-receptor
#8
Sean H White, Raymond M Sturgeon, Yueling Gu, Alysha Nensi, Neil S Magoski
Changes to neuronal activity often involve a rapid and precise transition from low to high excitability. In the marine snail, Aplysia, the bag cell neurons control reproduction by undergoing an afterdischarge, which begins with synaptic input releasing acetylcholine to open an ionotropic cholinergic receptor. Gating of this receptor causes depolarization and a shift from silence to continuous action potential firing, leading to the neuroendocrine secretion of egg-laying hormone and ovulation. At the onset of the afterdischarge, there is a rise in intracellular Ca2+, followed by both protein kinase C (PKC) activation and tyrosine dephosphorylation...
January 3, 2018: Neuroscience
https://www.readbyqxmd.com/read/29305938/ca2-dependent-potassium-channels-and-cannabinoid-signaling-in-the-endothelium-of-apolipoprotein-e-knockout-mice-before-plaque-formation
#9
Alexander I Bondarenko, Olga Panasiuk, Iryna Okhai, Fabrizio Montecucco, Karim J Brandt, François Mach
Endothelial Ca2+-dependent K+ channels (KCa) regulate endothelial function. We also know that stimulation of type 2 cannabinoid (CB2) receptors ameliorates atherosclerosis. However, whether atherosclerosis is accompanied by altered endothelial KCa- and CB2 receptor-dependent signaling is unknown. By utilizing an in situ patch-clamp approach, we directly evaluated the KCa channel function and the CB2 receptor-dependent electrical responses in the endothelium of aortic strips from young ApoE-/- and C57Bl/6 mice...
January 3, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29304162/adrenergic-receptors-inhibit-trpv1-activity-in-the-dorsal-root-ganglion-neurons-of-rats
#10
Yumi Matsushita, Miki Manabe, Naoki Kitamura, Izumi Shibuya
Transient receptor potential vanilloid type 1 (TRPV1) is a polymodal receptor channel that responds to multiple types of stimuli, such as heat, acid, mechanical pressure and some vanilloids. Capsaicin is the most commonly used vanilloid to stimulate TRPV1. TRPV1 channels are expressed in dorsal root ganglion neurons that extend to Aδ- and C-fibers and have a role in the transduction of noxious inputs to the skin into the electrical signals of the sensory nerve. Although noradrenergic nervous systems, including the descending antinociceptive system and the sympathetic nervous system, are known to modulate pain sensation, the functional association between TRPV1 and noradrenaline in primary sensory neurons has rarely been examined...
2018: PloS One
https://www.readbyqxmd.com/read/29303488/small-intestinal-ischemia-and-reperfusion-bioimpedance-measurements
#11
Runar James Strand-Amundsen, Christian Tronstad, Havard Kalvoy, Tom Erik Ruud, Jan Olav Hogetveit, Orjan Grottem Martinsen, Tor Inge Tønnessen
Trans-intestinal bioimpedance measurements have previously been used to investigate changes in electrical parameters during 6 hours of ischemia in the small intestine. Knowledge is lacking regarding the time course of trans-intestinal bioimpedance parameters during reperfusion. As reperfusion is an important part in the clinical treatment of intestinal ischemia, we need to know how it affects the bioimpedance measurements. Approach: We performed bioimpedance measurements, using a two-electrode setup on selected segments of the jejunum in 15 pigs...
January 5, 2018: Physiological Measurement
https://www.readbyqxmd.com/read/29302214/antidepressant-drug-paroxetine-blocks-the-open-pore-of-kv3-1-potassium-channel
#12
Hyang Mi Lee, Ok Hee Chai, Sang June Hahn, Bok Hee Choi
In patients with epilepsy, depression is a common comorbidity but difficult to be treated because many antidepressants cause pro-convulsive effects. Thus, it is important to identify the risk of seizures associated with antidepressants. To determine whether paroxetine, a very potent selective serotonin reuptake inhibitor (SSRI), interacts with ion channels that modulate neuronal excitability, we examined the effects of paroxetine on Kv3.1 potassium channels, which contribute to highfrequency firing of interneurons, using the whole-cell patch-clamp technique...
January 2018: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/29298898/a-triad-of-residues-is-functionally-transferrable-between-5-ht3-serotonin-receptors-and-nicotinic-acetylcholine-receptors
#13
Richard Mosesso, Dennis A Dougherty
Cys-loop receptors are pentameric ligand-gated ion channels that facilitate communication within the nervous system. Upon neurotransmitter binding, these receptors undergo an allosteric activation mechanism connecting the binding event to the membrane-spanning channel pore, which expands to conduct ions. Some of the earliest steps in this activation mechanism are carried out by residues proximal to the binding site, the relative positioning of which may reflect functional differences among members of the Cys-loop family of receptors...
January 3, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29289825/in-vitro-electroporation-detection-methods-an-overview
#14
REVIEW
Tina Batista Napotnik, Damijan Miklavčič
Exposing cells to an electric field leads to electroporation of the cell membrane which has already been explored and used in a number of applications in medicine and food biotechnology (e.g. electrochemotherapy, gene electrotransfer, extraction of biomolecules). The extent of electroporation depends on several conditions, including pulse parameters, types of cells and tissues, surrounding media, temperature etc. Each application requires a specific level of electroporation, so it must be explored in advance by employing methods for detecting electroporation...
December 16, 2017: Bioelectrochemistry
https://www.readbyqxmd.com/read/29289565/artifactual-hyperpolarization-during-extracellular-electrical-stimulation-proposed-mechanism-of-high-rate-neuromodulation-disproved
#15
L Stephen Lesperance, Milad Lankarany, Tianhe C Zhang, Rosana Esteller, Stéphanie Ratté, Steven A Prescott
BACKGROUND: Kilohertz-frequency electric field stimulation (kEFS) applied to the spinal cord can reduce chronic pain without causing the buzzing sensation (paresthesia) associated with activation of dorsal column fibers. This suggests that high-rate spinal cord stimulation (SCS) has a mode of action distinct from conventional, parasthesia-based SCS. A recent study reported that kEFS hyperpolarizes spinal neurons, yet this potentially transformative mode of action contradicts previous evidence that kEFS induces depolarization and was based on patch clamp recordings whose accuracy in the presence of kEFS has not been verified...
December 15, 2017: Brain Stimulation
https://www.readbyqxmd.com/read/29288665/intact-calcium-signaling-in-adrenergic-deficient-embryonic-mouse-hearts
#16
Jessica N Peoples, David G Taylor, Alexander N Katchman, Steven N Ebert
Mouse embryos that lack the ability to produce the adrenergic hormones, norepinephrine (NE) and epinephrine (EPI), due to disruption of the dopamine beta-hydroxylase (Dbh-/-) gene inevitably perish from heart failure during mid-gestation. Since adrenergic stimulation is well-known to enhance calcium signaling in developing as well as adult myocardium, and impairments in calcium signaling are typically associated with heart failure, we hypothesized that adrenergic-deficient embryonic hearts would display deficiencies in cardiac calcium signaling relative to adrenergic-competent controls at a developmental stage immediately preceding the onset of heart failure, which first appears beginning or shortly after mouse embryonic day 10...
December 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29283926/interactions-of-propofol-with-human-voltage-gated-kv1-5-channel-determined-by-docking-simulation-and-mutagenesis-analyses
#17
Akiko Kojima, Yutaka Fukushima, Yuki Ito, Wei-Guang Ding, Rika Ueda, Tomoyoshi Seto, Hirotoshi Kitagawa, Hiroshi Matsuura
Propofol blocks the voltage-gated human Kv1.5 (hKv1.5) channel by preferentially affecting in its open state. A previous mutational study suggested that several amino acids within the pore region of the hKv1.5 channel are involved in mediating the blocking action of propofol. The present investigation was undertaken to elucidate the predicted binding modes of propofol within the pore cavity of the open-state hKv1.5 channel, using computational docking and mutagenesis approaches. The docking simulation using a homology model of the hKv1...
January 2018: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/29278865/simvastatin-activates-single-skeletal-ryr1-channels-but-exerts-more-complex-regulation-of-the-cardiac-ryr2-isoform
#18
Elisa Venturi, Chris Lindsay, Sabine Lotteau, Zhaokang Yang, Emma Steer, Katja Witschas, Abigail D Wilson, James R Wickens, Angela J Russell, Derek Steele, Sarah Calaghan, Rebecca Sitsapesan
BACKGROUND AND PURPOSE: Statins are amongst the most widely prescribed drugs for those at risk of cardiovascular disease, lowering cholesterol levels by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Although effective in prevention of cardiovascular disease, statin use is associated with muscle weakness, myopathies and, in rare cases, fatal rhabdomyolysis. As simvastatin, a commonly prescribed statin, can promote Ca2+ release from sarcoplasmic reticulum (SR) vesicles, we investigated if simvastatin could directly activate skeletal (RyR1) and cardiac (RyR2) ryanodine receptors...
December 26, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29277899/proton-independent-activation-of-acid-sensing-ion-channel-asic3-by-alkaloid-lindoldhamine-from-laurus-nobilis
#19
Dmitry I Osmakov, Sergey G Koshelev, Yaroslav A Andreev, Maxim A Dubinnyi, Vadim S Kublitski, Roman G Efremov, Alexander I Sobolevsky, Sergey A Kozlov
BACKGROUND AND PURPOSE: Acid-sensing ion channels (ASICs) play an important role in synaptic plasticity and learning, as well as in nociception and mechanosensation. ASICs are implicated in pain, neurological and psychiatric diseases but their therapeutic potential is limited by lack of ligands activating them at physiological pH. EXPERIMENTAL APPROACH: Here we report extraction from laurel leaves, purification and structure determination of a bisbenzylisoquinoline alkaloid lindoldhamine (LIN) and characterization of its effect on ASIC3 channels using two-electrode voltage-clamp electrophysiological recordings from Xenopus laevis oocytes...
December 26, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29277715/direct-modification-of-the-5-ht3-receptor-current-by-some-anticancer-drugs
#20
Yukiko Nakamura, Yusuke Ishida, Makoto Kondo, Shoichi Shimada
The serotonin (5-hydroxytryptamine) type 3 (5-HT3) receptor is an important target in the control of emesis, and 5-HT3 receptor antagonists are effective against the early phase chemotherapy evoked vomiting. We recently reported that the anticancer drugs irinotecan and topotecan directly modulate the 5-HT-mediated 5-HT3 receptor current in vitro. In addition, the drug response depends on the 5-HT3 subunit composition. Here, we explored the effects of 35 anticancer drugs on the 5-HT3 receptor current. We microinjected Xenopus laevis oocytes with human 5-HT3A cRNA or a combination of human 5-HT3A and human 5-HT3B cRNA, and performed two-electrode voltage clamp recordings of 5-HT3A and 5-HT3AB receptor currents in the presence of each of the 35 drugs...
December 22, 2017: European Journal of Pharmacology
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