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Voltage Gated Calcium Channels

Laurent Ferron, Ivan Kadurin, Annette C Dolphin
Auxiliary α2 δ subunits are important proteins for trafficking of voltage-gated calcium channels (CaV ) at the active zones of synapses. We have previously shown that the post-translational proteolytic cleavage of α2 δ is essential for their modulatory effects on the trafficking of N-type (CaV 2.2) calcium channels (Kadurin et al. 2016). We extend these results here by showing that the probability of presynaptic vesicular release is reduced when an uncleaved α2 δ is expressed in rat neurons and that this inhibitory effect is reversed when cleavage of α2 δ is restored...
June 19, 2018: ELife
Per Hartvig Honoré, Anna Basnet, Pernille Kristensen, Lene Munkholm Andersen, Signe Neustrup, Pia Møllgaard, Laila Eljaja, Ole J Bjerrum
Introduction The pathophysiologic and neurochemical characteristics of neuropathic pain must be considered in the search for new treatment targets. Breakthroughs in the understanding of the structural and biochemical changes in neuropathy have opened up possibilities to explore new treatment paradigms. However, long term sequels from the damage are still difficult to treat. Aim of the study To examine the validity of pharmacological treatments in humans and animals for neuropathic pain. Method An overview from the literature and own experiences of pharmacological treatments employed to interfere in pain behavior in different animal models was performed...
December 29, 2017: Scandinavian Journal of Pain
M Saarnilehto, M Pekkanen-Mattila, K Aalto-Setälä, O Silvennoinen, A Koivisto
Aims Aim of the study was to characterize functional ion channel and GPCR responses by using selective pharmacological tools and intracellular calcium imaging from human inducible pluripotent stem cell-derived sensory neurons. Methods Sensory neurons were generated from human keratinocytes that were reprogrammed to inducible pluripotent stem cells by using standard Yamanaka factors. Inducible pluripotent stem cells were differentiated into sensory neurons by using 2 differentiation protocols (small molecule and PA6 co-culture)...
December 29, 2017: Scandinavian Journal of Pain
Fumiko Sekiguchi, Tomoyo Fujita, Takahiro Deguchi, Sakura Yamaoka, Ken Tomochika, Maho Tsubota, Sumire Ono, Yamato Horaguchi, Maki Ichii, Mio Ichikawa, Yumiko Ueno, Nene Koike, Tadatoshi Tanino, Huy Du Nguyen, Takuya Okada, Hiroyuki Nishikawa, Shigeru Yoshida, Tsuyako Ohkubo, Naoki Toyooka, Kazuya Murata, Hideaki Matsuda, Atsufumi Kawabata
Since Cav 3.2 T-type Ca2+ channels (T-channels) expressed in the primary afferents and CNS contribute to intractable pain, we explored T-channel-blocking components in distinct herbal extracts using a whole-cell patch-clamp technique in HEK293 cells stably expressing Cav 3.2 or Cav 3.1, and purified and identified sophoraflavanone G (SG) as an active compound from SOPHORAE RADIX (SR). Interestingly, hop-derived SG analogues, (2S)-6-prenylnaringenin (6-PNG) and (2S)-8-PNG, but not naringenin, also blocked T-channels; IC50 (μM) of SG, (2S)-6-PNG and (2S)-8-PNG was 0...
June 15, 2018: Neuropharmacology
J Su, A Delaney, R Matteo, B Bartlett, K Kultima, T Hökfelt, C I Svensson
Aims The lysophosphatidic acid (LPA) is an important mediator involved in neuropathic and bone cancer pain models. We are investigating if LPA is involved in arthritis-induced pain in the collagen antibody-induced arthritis (CAIA) mice model. Methods Arthritis was induced in male CBA mice by injection of 1.5 mg collagen type II antibody cocktail. Mechanical and thermal sensitivity and the degree of arthritis were assessed with von Frey filaments, Hargreaves box (heat), acetone test (cold) and visual scoring, respectively...
December 29, 2017: Scandinavian Journal of Pain
Tomić Maja, Pecikoza Uroš, Micov Ana, Vučković Sonja, Stepanović-Petrović Radica
Inflammatory pain is the most common type of pain that is treated clinically. The use of currently available treatments (classic analgesics - NSAIDs, paracetamol and opioids) is limited by insufficient efficacy and/or side effects/tolerance development. Antiepileptic drugs (AEDs) are widely used in neuropathic pain treatment, but there is substantial preclinical evidence on their efficacy against inflammatory pain, too. In this review we focus on gabapentinoids (gabapentin and pregabalin) and dibenzazepine AEDs (carbamazepine, oxcarbazepine, and recently introduced eslicarbazepine acetate) and their potential for relieving inflammatory pain...
June 15, 2018: Pharmacology & Therapeutics
Alexander Borst
Seeing the direction of motion is essential for survival of all sighted animals. Consequently, nerve cells that respond to visual stimuli moving in one but not in the opposite direction, so-called 'direction-selective' neurons, are found abundantly. In general, direction selectivity can arise by either signal amplification for stimuli moving in the cell's preferred direction ('preferred direction enhancement'), signal suppression for stimuli moving along the opposite direction ('null direction suppression'), or a combination of both...
June 13, 2018: PLoS Computational Biology
Joanna C Jen, Jijun Wan
Primary episodic ataxias (EAs) are a group of dominantly inherited disorders characterized by transient recurrent incoordination and truncal instability, often triggered by physical exertion and emotional stress, variably associated with progressive baseline ataxia. There are now eight designated subtypes based largely on genetic loci. Mutations have been identified in multiple individuals and families with EA1, EA2, and EA6, mostly with onset before adulthood. EA1 and EA2 are prototypical neurologic channelopathies...
2018: Handbook of Clinical Neurology
Anatoliy Maslyukov, Kaizhen Li, Xin Su, Yury Kovalchuk, Olga Garaschuk
Spontaneous neuronal activity and concomitant intracellular Ca2+ signaling are abundant during early perinatal development and are well known for their key role in neuronal proliferation, migration, differentiation and wiring. However, much less is known about the in vivo patterns of spontaneous Ca2+ signaling in immature adult-born cells. Here, by using two-photon Ca2+ imaging, we analyzed spontaneous in vivo Ca2+ signaling in adult-born juxtaglomerular cells of the mouse olfactory bulb over the time period of 5 weeks, from the day of their arrival in the glomerular layer till their stable integration into the preexisting neural network...
June 6, 2018: Cell Calcium
Richard Hw Funk
In this review we compile results cited in reliable journals that show a ratio for the use of pulsed electromagnetic fields (PEMF) in therapy, indeed. This is true especially for chronically inflamed joints. Furthermore, we try to link this therapeutic approach to the molecular background of chronic inflammation and arthritis. At first we start with the clinical outcome of PEMF therapy. Then, we look for possible triggers and an electromagnetic counterpart that is endogenously inherent in cell biology and in the tissues of interest...
2018: American Journal of Translational Research
Suellen Almeida-Corrêa, Michael Czisch, Carsten T Wotjak
Manganese-enhanced magnetic resonance imaging (MEMRI) is a powerful tool for in vivo non-invasive whole-brain mapping of neuronal activity. Mn2+ enters active neurons via voltage-gated calcium channels and increases local contrast in T1 -weighted images. Given the property of Mn2+ of axonal transport, this technique can also be used for tract tracing after local administration of the contrast agent. However, MEMRI is still not widely employed in basic research due to the lack of a complete description of the Mn2+ dynamics in the brain...
2018: Frontiers in Neural Circuits
Erum Rasheed, Jansen Seheult, James Gibney, Gerard Boran
Thyrotoxic periodic paralysis (TPP) is a rare complication of hyperthyroidism where increased influx of potassium into skeletal muscle cells leads to profound hypokalaemia and paralysis. Most cases arise sporadically in Asians however it is being increasingly reported in Caucasians. TPP is regarded as a channelopathy where a genetic and/or acquired defect in the sodium-potassium (Na+/K+-ATPase) pump renders it more sensitive to excess thyroid hormone in susceptible individuals. Because the clinical presentation is similar to familial hypokalaemic periodic paralysis (FHPP), genes implicated in this autosomal dominant condition became candidates for TPP, particularly if they were known to have thyroid hormone-responsive elements...
January 1, 2018: Annals of Clinical Biochemistry
Hanan Sayed Mohamed Farghaly, Israa El-Sayed Mohamed Ashry, Mohammad Salem Hareedy
BACKGROUND: Toxic effects of digoxin may occur with normal therapeutic serum level. However, the underlying mechanisms are not fully understood. Nuclear factor kappa-B (NF-kB) is an important transcription factor in most organ systems and is often implicated in the harmful effects of cardiac injury. NF-kB promotes inflammatory responses, mediates adverse cardiac remodeling and has a function correlation with calcium. The voltage-gated L-type calcium channel CaV1.2 mediates the influx of Ca+2 into the cell in response to membrane depolarization...
June 6, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Gamze Altun, Ömür Gülsüm Deniz, Kıymet Kübra Yurt, Devra Davis, Süleyman Kaplan
With current advances in technology, a number of epidemiological and experimental studies have reported a broad range of adverse effects of electromagnetic fields (EMF) on human health. Multiple cellular mechanisms have been proposed as direct causes or contributors to these biological effects. EMF-induced alterations in cellular levels can activate voltage-gated calcium channels and lead to the formation of free radicals, protein misfolding and DNA damage. Because rapidly dividing germ cells go through meiosis and mitosis, they are more sensitive to EMF in contrast to other slower-growing cell types...
May 16, 2018: Environmental Research
Zhen Xiao, Yunxiao Zhang, Jiao Zeng, Songping Liang, Cheng Tang, Zhonghua Liu
The venom of the spider Heteropoda venatoria produced lethal effect to cockroaches as reported in our previous study, and could be a resource for naturally-occurring insecticides. The present study characterized a novel cockroach voltage-gated sodium channels (NaV s) antagonist, μ-sparatoxin-Hv2 (μ-SPRTX-Hv2 for short), from this venom. μ-SPRTX-Hv2 is composed of 37 amino acids and contains six conserved cysteines. We synthesized the toxin by using the chemical synthesis method. The toxin was lethal to cockroaches when intraperitoneally injected, with a LD50 value of 2...
June 7, 2018: Toxins
Christine A Snidal, Qi Li, Brittany B Elliott, Henry K-H Mah, Robert H C Chen, Sabiha R Gardezi, Elise F Stanley
Neurotransmitter is released from presynaptic nerve terminals at fast-transmitting synapses by the action potential-gating of voltage dependent calcium channels (CaV), primarily of the CaV2.1 and CaV2.2 types. Entering Ca2+ diffuses to a nearby calcium sensor associated with a docked synaptic vesicle (SV) and initiates its fusion and discharge. Our previous findings that single CaVs can gate SV fusion argued for one or more tethers linking CaVs to docked SVs but the molecular nature of these tethers have not been established...
2018: Frontiers in Cellular Neuroscience
José F Ek-Vitorín, Tasha K Pontifex, Janis M Burt
Connexin 43 (Cx43), a gap junction protein seemingly fit to support cardiac impulse propagation and synchronic contraction, is phosphorylated in normoxia by casein kinase 1 (CK1). However, during cardiac ischemia or pressure overload hypertrophy, this phosphorylation fades, Cx43 abundance decreases at intercalated disks and increases at myocytes' lateral borders, and the risk of arrhythmia rises. Studies in wild-type and transgenic mice indicate that enhanced CK1-phosphorylation of Cx43 protects from arrhythmia, while dephosphorylation precedes arrhythmia vulnerability...
June 4, 2018: International Journal of Molecular Sciences
Rosa Ventura-Martínez, Guadalupe E Ángeles-López, Rodolfo Rodríguez, Ma Eva González-Trujano, Myrna Déciga-Campos
This study provides pharmacological evidence on the spasmolytic activity of Tagetes erecta L. (marigold or cempasúchil) on the guinea-pig ileum and presents data on its mechanism of action. The relaxant effect on KCl contractions was more marked with aqueous (AqEx) than with ethanol extracts (EtEx) of T. erecta flowers (55.6 ± 11.0 vs 21.1 ± 4.4%, respectively). In addition, the aqueous extract antagonized contractions elicited by EFS, but not by acetylcholine (73.5 ± 1.9 vs 14.5 ± 5.3%, respectively)...
July 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Nicholas W Bellono, Duncan B Leitch, David Julius
Ancient cartilaginous vertebrates, such as sharks, skates and rays, possess specialized electrosensory organs that detect weak electric fields and relay this information to the central nervous system1-4 . Sharks exploit this sensory modality for predation, whereas skates may also use it to detect signals from conspecifics 5 . Here we analyse shark and skate electrosensory cells to determine whether discrete physiological properties could contribute to behaviourally relevant sensory tuning. We show that sharks and skates use a similar low threshold voltage-gated calcium channel to initiate cellular activity but use distinct potassium channels to modulate this activity...
May 30, 2018: Nature
Glynis B Mattheisen, Timur Tsintsadze, Stephen M Smith
Voltage-gated sodium channels (VGSCs) are strategically positioned to mediate neuronal plasticity because of their influence on action potential waveform. VGSC function may be strongly inhibited by local anesthetic and antiepileptic drugs and modestly modulated via second messenger pathways. Here, we report that the allosteric modulators of the calcium-sensing receptor (CaSR) cinacalcet, calindol, calhex, and NPS 2143 completely inhibit VGSC current in the vast majority of cultured mouse neocortical neurons...
May 29, 2018: Cell Reports
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