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https://www.readbyqxmd.com/read/27911759/neurotransmitter-release-can-be-stabilized-by-a-mechanism-that-prevents-voltage-changes-near-the-end-of-action-potentials-from-affecting-calcium-currents
#1
Stephen G Clarke, Matthew S Scarnati, Kenneth G Paradiso
: At chemical synapses, presynaptic action potentials (APs) activate voltage-gated calcium channels, allowing calcium to enter and trigger neurotransmitter release. The duration, peak amplitude, and shape of the AP falling phase alter calcium entry, which can affect neurotransmitter release significantly. In many neurons, APs do not immediately return to the resting potential, but instead exhibit a period of depolarization or hyperpolarization referred to as an afterpotential. We hypothesized that presynaptic afterpotentials should alter neurotransmitter release by affecting the electrical driving force for calcium entry and calcium channel gating...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27908250/hypoglycemia-and-cardiac-arrhythmia-mechanisms-evidence-base-and-current-recommendations
#2
Sitara Gulrukh Khan, Mohammed Shahriar Huda
BACKGROUND: With the use of intensive insulin therapy and insulin secretagogues to optimize glycemic control in diabetes, hypoglycemia continues to present a clinical challenge. Hypoglycemia has been implicated in nocturnal sudden death in type 1 diabetes, and the mechanism underlying this is postulated to be cardiac arrhythmia. OBJECTIVE: This article reviews the evidence surrounding hypoglycemia and cardiac arrhythmia. METHODS: A structured search of the Pubmed bibliographic database was undertaken, and relevant peer-reviewed articles on the topic were included in the review...
December 1, 2016: Current Diabetes Reviews
https://www.readbyqxmd.com/read/27906869/early-and-sustained-vasopressin-infusion-augments-the-hemodynamic-efficacy-of-restrictive-fluid-resuscitation-and-improves-survival-in-a-liver-laceration-model-of-hemorrhagic-shock
#3
Raúl J Gazmuri, Kasen Whitehouse, Kruti Shah, Karla Whittinghill, Alvin Baetiong, Jeejabai Radhakrishnan
BACKGROUND: Current management of hemorrhagic shock favors restrictive fluid resuscitation before control of the bleeding source. We investigated the additional effects of early and sustained vasopressin infusion in a swine model of hemorrhagic shock produced by liver laceration. METHODS: Forty male domestic pigs (32 to 40 kg) had a liver laceration inflicted with an X-shaped blade clamp, 32 received a second laceration at minute 7.5, and 24 received two additional lacerations at minute 15...
November 30, 2016: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/27906053/attenuated-ca-2-release-in-a-mouse-model-of-limb-girdle-muscular-dystrophy-2a
#4
Marino DiFranco, Irina Kramerova, Julio L Vergara, Melissa Jan Spencer
BACKGROUND: Mutations in CAPN3 cause limb girdle muscular dystrophy type 2A (LGMD2A), a progressive muscle wasting disease. CAPN3 is a non-lysosomal, Ca-dependent, muscle-specific proteinase. Ablation of CAPN3 (calpain-3 knockout (C3KO) mice) leads to reduced ryanodine receptor (RyR1) expression and abnormal Ca2+/calmodulin-dependent protein kinase II (Ca-CaMKII)-mediated signaling. We previously reported that Ca(2+) release measured by fura2-FF imaging in response to single action potential stimulation was reduced in old C3KO mice; however, the use of field stimulation prevented investigation of the mechanisms underlying this impairment...
February 24, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27901080/block-of-nicotinic-acetylcholine-receptors-by-philanthotoxins-is-strongly-dependent-on-their-subunit-composition
#5
Hamid S Kachel, Rohit N Patel, Henrik Franzyk, Ian R Mellor
Philanthotoxin-433 (PhTX-433) is an active component of the venom from the Egyptian digger wasp, Philanthus triangulum. PhTX-433 inhibits several excitatory ligand-gated ion channels, and to improve selectivity two synthetic analogues, PhTX-343 and PhTX-12, were developed. Previous work showed a 22-fold selectivity of PhTX-12 over PhTX-343 for embryonic muscle-type nicotinic acetylcholine receptors (nAChRs) in TE671 cells. We investigated their inhibition of different neuronal nAChR subunit combinations as well as of embryonic muscle receptors expressed in Xenopus oocytes...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899943/effects-of-allitridum-on-the-transient-outward-potassium-current-in-rats-with-heart-failure
#6
Xiao-Jing Zhao, Kun Lin, Yu Zhang, Bin Xu, Li Liu, Yi-Cheng Fu, Xi Chen, Zhong-Qi Cai, Zhi-Juan Wu, Yun Huang, Yang Li
OBJECTIVE: To study the effect of allitridum on the transient outward potassium current (Ito) of ventricular myocytes in heart failure (HF). METHODS: The dual enzymatic method was used to separate single ventricular myocytes from Sprague Dawley rats. Patch-clamping was used to record Ito and analyze the effect of allitridum on the current. RESULTS: The Ito current had a significant decrease in the HF group, compared with the control group...
September 2016: Journal of Geriatric Cardiology: JGC
https://www.readbyqxmd.com/read/27898427/cocaine-withdrawal-reduces-gamma-aminobutyric-acid-ergic-transmission-and-gephyrin-expression-at-medial-prefrontal-cortex-in-cocaine-conditioned-place-preference-rats-which-shows-increased-cocaine-seeking
#7
Wenqiong Yang, Hongsheng He, Yan Pan, Falan Duan, Dan Zhao, Bo Hu, Qingzhen Zhou, Wanhong Liu
AIMS: Chronic cocaine abuse decreases the inhibitory synaptic transmission via unknown mechanisms, while pharmacologically augmenting gamma-aminobutyric acid-ergic (GABAergic) transmission attenuates cocaine craving. Here, we propose that prolonged cocaine withdrawal downregulates GABAergic transmission and its important regulator gephyrin in medial prefrontal cortex (mPFC), in cocaine-conditioned place-preference (CPP) rats. METHODS: CPP test, patch clamp, and Western blot analysis are engaged to test this proposal...
November 30, 2016: European Addiction Research
https://www.readbyqxmd.com/read/27896651/postnatal-administration-of-dizocilpine-inhibits-neuronal-excitability-in-pfc-and-induces-social-deficits-detected-by-miceprofiler
#8
Dexiao Zhu, Hui Wang, Jintao Wu, Qian Wang, Ling Xu, Yue Zhao, Kunkun Pang, Qingqing Shi, Wenbo Zhao, Jing Zhang, Jinhao Sun
Schizophrenia is a devastating mental disease with social deficit as its core component of negative symptoms, which could be induced in rodents by dizocilpine (MK-801), a noncompetitive NMDA receptor antagonist. NMDA receptors are highly expressed during the postnatal period. However, less attention has been paid to the effects of postnatal MK-801 administration on social interaction. In this study, we evaluated the effects of postnatal administration of MK-801 on social interaction and explored the possible mechanisms...
November 28, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27889432/decrease-of-high-voltage-ca-2-currents-in-the-dentate-gyrus-granule-cells-by-entorhinal-amyloidopathy-is-reversed-by-calcium-channel-blockade
#9
Hamid Gholami Pourbadie, Nima Naderi, Hadi Mirzapour Delavar, Mahshid Hosseinzadeh, Nasrin Mehranfard, Fariba Khodagholi, Mahyar Janahmadi, Fereshteh Motamedi
In the Alzheimer's disease (AD), entorhinal-hippocampal circuit is one of the earliest affected networks. There are some evidences indicating abnormal neuronal excitability and impaired synaptic plasticity in the dentate gyrus (DG) of AD animal model. However, the underlying mechanism leading to DG dysfunction particularly in the early phase of AD is not known. Since calcium dyshomeostasis has a critical role in the etiology of AD, it is possible that this phenomenon precedes electrophysiological alteration in the DG...
November 24, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27888095/modulation-of-voltage-gated-conductances-of-retinal-horizontal-cells-by-uv-excited-tio2-nanoparticles
#10
Xenia Meshik, Min Choi, Adam Baker, R Paul Malchow, Leigha Covnot, Samuel Doan, Souvik Mukherjee, Sidra Farid, Mitra Dutta, Michael A Stroscio
This study examines the ability of optically-excited titanium dioxide nanoparticles to influence voltage-gated ion channels in retinal horizontal cells. Voltage clamp recordings were obtained in the presence and absence of TiO2 and ultraviolet laser excitation. Significant current changes were observed in response to UV light, particularly in the -40 mV to +40 mV region where voltage-gated Na(+) and K(+) channels have the highest conductance. Cells in proximity to UV-excited TiO2 exhibited a left-shift in the current-voltage relation of around 10 mV in the activation of Na(+) currents...
November 22, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/27886375/modulation-of-chloride-currents-in-human-lung-epithelial-cells-exposed-to-exogenous-oxidative-stress
#11
Rita Canella, Marta Martini, Roberta Borriello, Carlotta Cavicchio, Ximena M Muresan, Mascia Benedusi, Franco Cervellati, Giuseppe Valacchi
Air pollution continues to be a major public health concern affecting 9 out of 10 individuals living in urban areas worldwide. Respiratory tract is the organ most exposed to gas pollution and ozone has been shown to be one of the most noxious pollutants to which living organisms are exposed. In the present work, we have investigated the effects of 0.1 ppm of ozone on chloride currents in human lung epithelial cells (A549 line) and whether this effect could be modulated by vitamin E pre-treatment. Whole-cell patch clamp technique was applied to not excitable cells in order to obtain information about chloride currents behavior, important for epithelial lung cells homeostasis...
November 25, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27884956/regional-effects-of-streptozotocin-induced-diabetes-on-shortening-and-calcium-transport-in-epicardial-and-endocardial-myocytes-from-rat-left-ventricle
#12
Manal M A Smail, Muhammad A Qureshi, Anatoliy Shmygol, Murat Oz, Jaipaul Singh, Vadym Sydorenko, Alya Arabi, Frank C Howarth, Lina Al Kury
In the heart, the left ventricle pumps blood at higher pressure than the right ventricle. Within the left ventricle, the electromechanical properties of ventricular cardiac myocytes vary transmurally and this may be related to the gradients of stress and strain experienced in vivo across the ventricular wall. Diabetes is also associated with alterations in hemodynamic function. The aim of this study was to investigate shortening and Ca(2+) transport in epicardial (EPI) and endocardial (ENDO) left ventricular myocytes in the streptozotocin (STZ)-induced diabetic rat...
November 2016: Physiological Reports
https://www.readbyqxmd.com/read/27881786/neuronal-dysfunction-in-ipsc-derived-medium-spiny-neurons-from-chorea-acanthocytosis-patients-is-reversed-by-src-kinase-inhibition-and-f-actin-stabilization
#13
Nancy Stanslowsky, Peter Reinhardt, Hannes Glass, Norman Kalmbach, Maximilian Naujock, Niko Hensel, Verena Lübben, Arun Pal, Anna Venneri, Francesca Lupo, Lucia De Franceschi, Peter Claus, Jared Sterneckert, Alexander Storch, Andreas Hermann, Florian Wegner
: Chorea-acanthocytosis (ChAc) is a fatal neurological disorder characterized by red blood cell acanthocytes and striatal neurodegeneration. Recently, severe cell membrane disturbances based on depolymerized cortical actin and an elevated Lyn kinase activity in erythrocytes from ChAc patients were identified. How this contributes to the mechanism of neurodegeneration is still unknown. To gain insight into the pathophysiology, we established a ChAc patient-derived induced pluripotent stem cell model and an efficient differentiation protocol providing a large population of human striatal medium spiny neurons (MSNs), the main target of neurodegeneration in ChAc...
November 23, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27881784/low-somatic-sodium-conductance-enhances-action-potential-precision-in-time-coding-auditory-neurons
#14
Yang Yang, Bina Ramamurthy, Andreas Neef, Matthew A Xu-Friedman
: Auditory nerve fibers encode sounds in the precise timing of action potentials (APs), which is used for such computations as sound localization. Timing information is relayed through several cell types in the auditory brainstem that share an unusual property: their APs are not overshooting, suggesting that the cells have very low somatic sodium conductance (gNa). However, it is not clear how gNa influences temporal precision. We addressed this by comparing bushy cells (BCs) in the mouse cochlear nucleus with T-stellate cells (SCs), which do have normal overshooting APs...
November 23, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27878566/pharmacokinetic-and-pharmacodynamic-properties-of-faster-acting-insulin-aspart-versus-insulin-aspart-across-a-clinically-relevant-dose-range-in-subjects-with-type-1-diabetes-mellitus
#15
Tim Heise, Kirstine Stender-Petersen, Ulrike Hövelmann, Jacob Bonde Jacobsen, Leszek Nosek, Eric Zijlstra, Hanne Haahr
BACKGROUND: Absorption of current rapid-acting insulins is too slow for patients with diabetes mellitus to achieve optimal postprandial glucose control. Faster-acting insulin aspart (faster aspart) is insulin aspart in a new formulation with faster early absorption. We compared the pharmacokinetic/pharmacodynamic properties of faster aspart and insulin aspart across a clinically relevant dose range. METHODS: In this randomised, double-blind, crossover trial, 46 subjects with type 1 diabetes mellitus received single subcutaneous doses of faster aspart and insulin aspart at 0...
November 22, 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/27877113/the-effects-of-realistic-synaptic-distribution-and-3d-geometry-on-signal-integration-and-extracellular-field-generation-of-hippocampal-pyramidal-cells-and-inhibitory-neurons
#16
Attila I Gulyás, Tamás F Freund, Szabolcs Káli
In vivo and in vitro multichannel field and somatic intracellular recordings are frequently used to study mechanisms of network pattern generation. When interpreting these data, neurons are often implicitly considered as electrotonically compact cylinders with a homogeneous distribution of excitatory and inhibitory inputs. However, the actual distributions of dendritic length, diameter, and the densities of excitatory and inhibitory input are non-uniform and cell type-specific. We first review quantitative data on the dendritic structure and synaptic input and output distribution of pyramidal cells (PCs) and interneurons in the hippocampal CA1 area...
2016: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/27866274/ryanodine-receptor-type-3-does-not-contribute-to-contractions-in-the-mouse-myometrium-regardless-of-pregnancy
#17
Katsuhito Matsuki, Masashi Takemoto, Yoshiaki Suzuki, Hisao Yamamura, Susumu Ohya, Hiroshi Takeshima, Yuji Imaizumi
Ryanodine receptor type 3 (RyR3) is expressed in myometrial smooth muscle cells (MSMCs). The short isoform of RyR3 is a dominant negative variant (DN-RyR3) and negatively regulates the functions of RyR2 and full-length (FL)-RyR3. DN-RyR3 has been suggested to function as a major RyR3 isoform in non-pregnant (NP) mouse MSMCs, and FL-RyR3 may also be upregulated during pregnancy (P). This increase in the FL-RyR3/DN-RyR3 ratio may contribute to the strong contractions by MSMCs for parturition. In the present study, spontaneous contractions by the myometrium in NP and P mice were highly susceptible to nifedipine but were not affected by ryanodine...
November 20, 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27864845/activity-of-the-anticonvulsant-lacosamide-in-experimental-and-human-epilepsy-via-selective-effects-on-slow-na-channel-inactivation
#18
Dominik Holtkamp, Thoralf Opitz, Isabelle Niespodziany, Christian Wolff, Heinz Beck
OBJECTIVE: In human epilepsy, pharmacoresistance to antiepileptic drug therapy is a major problem affecting ~30% of patients with epilepsy. Many classical antiepileptic drugs target voltage-gated sodium channels, and their potent activity in inhibiting high-frequency firing has been attributed to their strong use-dependent blocking action. In chronic epilepsy, a loss of use-dependent block has emerged as a potential cellular mechanism of pharmacoresistance for anticonvulsants acting on voltage-gated sodium channels...
November 19, 2016: Epilepsia
https://www.readbyqxmd.com/read/27864268/de-novo-gabrg2-mutations-associated-with-epileptic-encephalopathies
#19
Dingding Shen, Ciria C Hernandez, Wangzhen Shen, Ningning Hu, Annapurna Poduri, Beth Shiedley, Alex Rotenberg, Alexandre N Datta, Steffen Leiz, Steffi Patzer, Rainer Boor, Kerri Ramsey, Ethan Goldberg, Ingo Helbig, Xilma R Ortiz-Gonzalez, Johannes R Lemke, Eric D Marsh, Robert L Macdonald
Epileptic encephalopathies are a devastating group of severe childhood onset epilepsies with medication-resistant seizures and poor developmental outcomes. Many epileptic encephalopathies have a genetic aetiology and are often associated with de novo mutations in genes mediating synaptic transmission, including GABAA receptor subunit genes. Recently, we performed next generation sequencing on patients with a spectrum of epileptic encephalopathy phenotypes, and we identified five novel (A106T, I107T, P282S, R323W and F343L) and one known (R323Q) de novo GABRG2 pathogenic variants (mutations) in eight patients...
November 17, 2016: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/27863381/probucol-prevents-atrial-ion-channel-remodeling-in-an-alloxan-induced-diabetes-rabbit-model
#20
Huaying Fu, Guangping Li, Changle Liu, Jian Li, Lijun Cheng, Wansong Yang, Gary Tse, Jichao Zhao, Tong Liu
Diabetes mellitus (DM) increases the risk of developing atrial fibrillation (AF), but the molecular mechanisms of diabetes-induced atrial remodeling processes have not been fully characterized. The aim of this study was to examine the mechanisms underlying atrial ion channel remodeling in alloxan-induced diabetes model in rabbits. A total of 40 Japanese rabbits were randomly assigned to a control group (C), alloxan-induced diabetic group (DM), probucol-treated control group (Control-P), and probucol-treated diabetic group (DM-P)...
November 14, 2016: Oncotarget
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