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P/q type calcium channels

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https://www.readbyqxmd.com/read/28411270/short-term-facilitation-at-a-detonator-synapse-requires-the-distinct-contribution-of-multiple-types-of-voltage-gated-calcium-channels
#1
Simon Chamberland, Alesya Evstratova, Katalin Tóth
Neuronal calcium elevations are shaped by several key parameters, including the properties, density, and the spatial location of voltage-gated calcium channels (VGCCs). These features allow presynaptic terminals to translate complex firing frequencies and tune the amount of neurotransmitter released. While synchronous neurotransmitter release relies on both P/Q- and N-type VGCCs at hippocampal MF-CA3 synapses, the specific contribution of VGCCs to calcium dynamics, neurotransmitter release and short-term facilitation remains unknown...
April 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28371832/timed-sequential-therapy-of-the-selective-t-type-calcium-channel-blocker-mibefradil-and-temozolomide-in-patients-with-recurrent-high-grade-gliomas
#2
Matthias Holdhoff, Xiaobu Ye, Jeffrey G Supko, Louis B Nabors, Arati S Desai, Tobias Walbert, Glenn J Lesser, William L Read, Frank S Lieberman, Martin A Lodge, Jeffrey Leal, Joy D Fisher, Serena Desideri, Stuart A Grossman, Richard L Wahl, David Schiff
Background.: Mibefradil (MIB), previously approved for treatment of hypertension, is a selective T-type calcium channel blocker with preclinical activity in high-grade gliomas (HGGs). To exploit its presumed mechanism of impacting cell cycle activity (G1 arrest), we designed a phase I study to determine safety and the maximum tolerated dose (MTD) of MIB when given sequentially with temozolomide (TMZ) in recurrent (r)HGG. Methods.: Adult patients with rHGG ≥3 months from TMZ for initial therapy received MIB in 4 daily doses (q...
March 22, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28348377/bilirubin-augments-ca-2-load-of-developing-bushy-neurons-by-targeting-specific-subtype-of-voltage-gated-calcium-channels
#3
Min Liang, Xin-Lu Yin, Hai-Bo Shi, Chun-Yan Li, Xin-Yi Li, Ning-Ying Song, Hao-Song Shi, Yi Zhao, Lu-Yang Wang, Shan-Kai Yin
Neonatal brain is particularly vulnerable to pathological levels of bilirubin which elevates and overloads intracellular Ca(2+), leading to neurotoxicity. However, how voltage-gated calcium channels (VGCCs) are functionally involved in excess calcium influx remains unknown. By performing voltage-clamp recordings from bushy cells in the ventral cochlear nucleus (VCN) in postnatal rat pups (P4-17), we found the total calcium current density was more than doubled over P4-17, but the relative weight of VGCC subtypes changed dramatically, being relatively equal among T, L, N, P/Q and R-type at P4-6 to predominantly L, N, R over T and P/Q at P15-17...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28330839/evolutionary-insights-into-t-type-ca-2-channel-structure-function-and-ion-selectivity-from-the-trichoplax-adhaerens-homologue
#4
Carolyn L Smith, Salsabil Abdallah, Yuen Yan Wong, Phuong Le, Alicia N Harracksingh, Liana Artinian, Arianna N Tamvacakis, Vincent Rehder, Thomas S Reese, Adriano Senatore
Four-domain voltage-gated Ca(2+) (Cav) channels play fundamental roles in the nervous system, but little is known about when or how their unique properties and cellular roles evolved. Of the three types of metazoan Cav channels, Cav1 (L-type), Cav2 (P/Q-, N- and R-type) and Cav3 (T-type), Cav3 channels are optimized for regulating cellular excitability because of their fast kinetics and low activation voltages. These same properties permit Cav3 channels to drive low-threshold exocytosis in select neurons and neurosecretory cells...
April 3, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28290248/the-%C3%AE-2%C3%AE-subunit-and-absence-epilepsy-beyond-calcium-channels
#5
Roberta Celli, Ines Santolini, Michela Guiducci, Gilles van Luijtelaar, Pasquale Parisi, Pasquale Striano, Roberto Gradini, Giuseppe Battaglia, Richard T Ngomba, Ferdinando Nicoletti
Spike-wave discharges, underlying absence seizures, are generated within a cortico-thalamo-cortical network that involves the somatosensory cortex, the reticular thalamic nucleus, and the ventrobasal thalamic nuclei. Activation of T-type voltage-sensitive calcium channels (VSCCs) contributes to the pathological oscillatory activity of this network, and some of the first-line drugs used in the treatment of absence epilepsy inhibit T-type calcium channels. The α2δ subunit is a component of high voltage-activated VSCCs (i...
March 8, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28223480/in-vivo-imaging-reveals-that-pregabalin-inhibits-cortical-spreading-depression-and-propagation-to-subcortical-brain-structures
#6
Stuart M Cain, Barry Bohnet, Jeffrey LeDue, Andrew C Yung, Esperanza Garcia, John R Tyson, Sascha R A Alles, Huili Han, Arn M J M van den Maagdenberg, Piotr Kozlowski, Brian A MacVicar, Terrance P Snutch
Migraine is characterized by severe headaches that can be preceded by an aura likely caused by cortical spreading depression (SD). The antiepileptic pregabalin (Lyrica) shows clinical promise for migraine therapy, although its efficacy and mechanism of action are unclear. As detected by diffusion-weighted MRI (DW-MRI) in wild-type (WT) mice, the acute systemic administration of pregabalin increased the threshold for SD initiation in vivo. In familial hemiplegic migraine type 1 mutant mice expressing human mutations (R192Q and S218L) in the CaV2...
February 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28202361/pre-clinical-evaluation-of-voltage-gated-calcium-channel-blockers-derived-from-the-spider-p-%C3%A2-nigriventer-in-glioma-progression
#7
Natália Fontana Nicoletti, Thaís Cristina Erig, Rafael Fernandes Zanin, Marcelo Ricardo Roxo, Nelson Pires Ferreira, Marcus Vinicius Gomez, Fernanda Bueno Morrone, Maria Martha Campos
This study investigated the effects of P/Q- and N-type voltage-gated calcium channel (VGCC) blockers derived from P. nigriventer in glioma progression, by means of in vitro and in vivo experiments. Glioma cells M059J, U-138MG and U-251MG were used to evaluate the antiproliferative effects of P/Q- and N-type VGCC inhibitors PhTx3-3 and Phα1β from P. nigriventer (0.3-100 pM), in comparison to MVIIC and MVIIA from C. magus (0.3-100 pM), respectively. The toxins were also analyzed in a glioma model induced by implantation of GL261 mouse cells...
February 13, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28167673/ubiquitin-ligase-rnf138-promotes-episodic-ataxia-type-2-associated-aberrant-degradation-of-human-cav2-1-p-q-type-calcium-channels
#8
Ssu-Ju Fu, Chung-Jiuan Jeng, Chia-Hao Ma, Yi-Jheng Peng, Chi-Ming Lee, Ya-Ching Fang, Yi-Ching Lee, Sung-Chun Tang, Meng-Chun Hu, Chih-Yung Tang
Voltage-gated CaV2.1 channels comprise a pore-forming α1A (CaV2.1) subunit with auxiliary α2δ and β subunits. CaV2.1 channels play an essential role in regulating synaptic signaling. Mutations in the human gene encoding CaV2.1 subunit are associated with the cerebellar disease episodic ataxia type 2 (EA2). Several EA2-causing mutants exhibit impaired protein stability and exert dominant-negative suppression of CaV2.1 wild-type (WT) protein expression via aberrant proteasomal degradation. Herein we set out to delineate the protein degradation mechanism of human CaV2...
February 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28096552/novel-missense-variant-of-cacna1a-gene-in-a-slovak-family-with-episodic-ataxia-type-2
#9
Andrea Petrovicova, Miroslav Brozman, Egon Kurca, Tibor Gobo, Jana Dluha, Klaudia Kalmarova, Vladimir Nosal, Martina Hikkelova, Adriana Krajciova, Tatiana Burjanivova, Stefan Sivak
INTRODUCTION: Episodic ataxias (EAs) are rare dominantly inherited neurological disorders characterized by recurrent episodes of ataxia lasting minutes to hours. The most common subtype is EA type 2 (EA2) caused by pathogenic variants of calcium voltage-gated channel subunit alpha1 A gene (CACNA1A) on chromosome 19p13. SUBJECTS AND METHODS: We examined a Slovak three-generation family. Genomic DNA of the family members was extracted from peripheral blood and amplified by polymerase chain reaction...
January 13, 2017: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
https://www.readbyqxmd.com/read/28093215/melanocortin-4-receptor-constitutive-activity-inhibits-l-type-voltage-gated-calcium-channels-in-neurons
#10
F Agosti, S Cordisco Gonzalez, V Martinez Damonte, M J Tolosa, N Di Siervi, H B Schioth, C Davio, M Perello, J Raingo
The melanocortin 4 receptor (MC4R) is a G protein-coupled receptor (GPCR) that is expressed in several brain nuclei playing a crucial role in the regulation of energy balance controlling the homeostasis of the organism. It displays both agonist-evoked and constitutive activity, and moreover, it can couple to different G proteins. Most of the research on MC4R has been focused on agonist-induced activity, while the molecular and cellular basis of MC4R constitutive activity remains scarcely studied. We have previously shown that neuronal N-type voltage-gated calcium channels (CaV2...
January 16, 2017: Neuroscience
https://www.readbyqxmd.com/read/28078065/clinical-features-of-neuromuscular-disorders-in-patients-with-n-type-voltage-gated-calcium-channel-antibodies
#11
Andreas Totzeck, Petra Mummel, Oliver Kastrup, Tim Hagenacker
Neuromuscular junction disorders affect the pre- or postsynaptic nerve to muscle transmission due to autoimmune antibodies. Members of the group like myasthenia gravis and Lambert-Eaton syndrome have pathophysiologically distinct characteristics. However, in practice, distinction may be difficult. We present a series of three patients with a myasthenic syndrome, dropped-head syndrome, bulbar and respiratory muscle weakness and positive testing for anti-N-type voltage-gated calcium channel antibodies. In two cases anti-acetylcholin receptor antibodies were elevated, anti-P/Q-type voltage-gated calcium channel antibodies were negative...
September 15, 2016: European Journal of Translational Myology
https://www.readbyqxmd.com/read/27857685/conditional-knockout-of-cav2-1-disrupts-the-accuracy-of-spatial-recognition-of-ca1-place-cells-and-spatial-contextual-recognition-behavior
#12
Dahee Jung, Yu J Hwang, Hoon Ryu, Masanobu Kano, Kenji Sakimura, Jeiwon Cho
Hippocampal pyramidal neurons play an essential role in processing spatial information as implicated with its place-dependent firing. Although, previous slice physiology studies have reported that voltage gated calcium channels contribute to spike shapes and corresponding firing rate in the hippocampus, the roles of P/Q type calcium channels (Cav2.1) underlying neural activity in behaving mice have not been well-investigated. To determine physiological and behavioral roles of Cav2.1, we conducted place cell recordings in CA1 and hippocampus dependent learning/memory tasks using mice lacking Cav2...
2016: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/27823926/cisplatin-induced-neuropathic-pain-is-mediated-by-upregulation-of-n-type-voltage-gated-calcium-channels-in-dorsal-root-ganglion-neurons
#13
Markus Leo, Linda-Isabell Schmitt, Martin Erkel, Margarita Melnikova, Jürgen Thomale, Tim Hagenacker
Cisplatin is important in the treatment of various types of cancer. Although it is highly effective, it also has severe side effects, with neurotoxicity in dorsal root ganglion (DRG) neurons being one of the most common. The key mechanisms of neurotoxicity are still controversially discussed; however, disturbances of the calcium homeostasis in DRG neurons have been suggested to mediate cisplatin neurotoxicity. By using the whole-cell patch-clamp technique, immunostaining and behavioral experiments with Sprague-Dawley rats, we examined the influence of short- and long-term exposure to cisplatin on voltage-gated calcium channel (VGCC) currents (ICa(V)) in small DRG neurons...
February 2017: Experimental Neurology
https://www.readbyqxmd.com/read/27806289/vulnerability-of-purkinje-cells-generated-from-spinocerebellar-ataxia-type-6-patient-derived-ipscs
#14
Yoshihito Ishida, Hideshi Kawakami, Hiroyuki Kitajima, Ayaka Nishiyama, Yoshiki Sasai, Haruhisa Inoue, Keiko Muguruma
Spinocerebellar ataxia type 6 (SCA6) is a dominantly inherited neurodegenerative disease characterized by loss of Purkinje cells in the cerebellum. SCA6 is caused by CAG trinucleotide repeat expansion in CACNA1A, which encodes Cav2.1, α1A subunit of P/Q-type calcium channel. However, the pathogenic mechanism and effective therapeutic treatments are still unknown. Here, we have succeeded in generating differentiated Purkinje cells that carry patient genes by combining disease-specific iPSCs and self-organizing culture technologies...
November 1, 2016: Cell Reports
https://www.readbyqxmd.com/read/27744004/histamine-h3-receptor-activation-stimulates-calcium-mobilization-in-a-subpopulation-of-rat-striatal-neurons-in-primary-culture-but-not-in-synaptosomes
#15
Nayeli Rivera-Ramírez, Wilber Montejo-López, María-Cristina López-Méndez, Agustín Guerrero-Hernández, Anayansi Molina-Hernández, Ubaldo García-Hernández, José-Antonio Arias-Montaño
The histamine H3 receptor (H3R) is abundantly expressed in the Central Nervous System where it regulates several functions pre and postsynaptically. H3Rs couple to Gαi/o proteins and trigger or modulate several intracellular signaling pathways, including the cAMP/PKA pathway and the opening of N- and P/Q-type voltage-gated Ca(2+) channels. In transfected cells, activation of the human H3R of 445 amino acids (hH3R445) results in phospholipase C (PLC) stimulation and release of Ca(2+) from intracellular stores...
December 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27625130/-study-on-the-electrophsiological-properties-in-the-stria-vascularis-pericytes-in-cochlear-of-guinea-pig
#16
Y H Liu, Y P Wang, Y Wang, K T Ma, J Q Si, L Li
OBJECTIVE: The purpose of this paper was to study the electrophysiological properties and the type of potassium channels on cell membrane in the stria vascularis pericytes in cochlear of guinea pig. METHODS: Firstly examined the expression of the stria vascularis pericytes by desmin, a marker of pericytes, in cochlear of guinea pig with immunofluorescent method. Using whole-cell patch clamp recording techniques to observe electrophysiological properties in the cochlear pericytes in stria vascularis of guinea pig...
August 7, 2016: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
https://www.readbyqxmd.com/read/27597561/teaching-video-neuroimages-p-q-type-voltage-gated-calcium-channel-associated-paraneoplastic-elliptical-nystagmus
#17
Eva A Mistry, Andrew G Lee, Eugene C Lai
No abstract text is available yet for this article.
September 6, 2016: Neurology
https://www.readbyqxmd.com/read/27586650/upregulation-of-l-type-calcium-channels-in-colonic-inhibitory-motoneurons-of-p-q-type-calcium-channel-deficient-mice
#18
Eileen Rodriguez-Tapia, Alberto Perez-Medina, Xiaochun Bian, James J Galligan
Enteric inhibitory motoneurons use nitric oxide and a purine neurotransmitter to relax gastrointestinal smooth muscle. Enteric P/Q-type Ca(2+) channels contribute to excitatory neuromuscular transmission; their contribution to inhibitory transmission is less clear. We used the colon from tottering mice (tg/tg, loss of function mutation in the α1A pore-forming subunit of P/Q-type Ca(2+) channels) to test the hypothesis that P/Q-type Ca(2+) channels contribute to inhibitory neuromuscular transmission and colonic propulsive motility...
October 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27581393/neural-cell-proliferation-and-survival-in-the-hippocampus-of-adult-cav-2-1-calcium-ion-channel-mutant-mice
#19
Fikru Nigussie, Pei-San Huang, Kris Lukauskis, Bhupinder Bawa, Eid Moussa, Louise C Abbott
Tottering mutant mice carry a mutation in the pore-forming subunit (α1A) of CaV2.1 (P/Q-type) voltage-gated calcium ion (Ca(2+)) channels resulting in reduced neuronal Ca(2+) current density. We assessed male tottering mice for spatial learning using the Morris water maze. Tottering mice performed worse than wild type mice, suggesting abnormal hippocampal function. Because Ca(2+) influx via voltage-dependent Ca(2+) channels regulates neuronal survival and function, we assessed hippocampus volume and cell density using hematoxylin and eosin stained serial sections...
November 1, 2016: Brain Research
https://www.readbyqxmd.com/read/27530945/-composition-of-potassium-channels-in-normal-rat-coronary-smooth-muscle-cells-and-activation-effects-of-docosahexaenoic-acid
#20
L L Qian, R X Wang, M Q Sun, D Y Xia, X Tang, Y Ji, Y Wu, X Y Liu, S P Dang, Q Chai, T Lu
OBJECTIVE: To investigate the composition of potassium channels in normal rat coronary smooth muscle cells (CASMCs) and the activation effects of docosahexaenoic acid (DHA). METHODS: CASMCs were isolated by enzyme digestion.Effects of different types of potassium channel blockers and/or DHA on potassium channels currents were studied by whole-cell patch clamp technique. RESULTS: Potassium currents were significantly increased with 5 μmol/L DHA perfusion (P<0...
July 24, 2016: Zhonghua Xin Xue Guan Bing za Zhi
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