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Voltage-dependent calcium channels

Lucía Isidoro, Mercedes Ferrer, Mercedes Perusquía
BACKGROUND: Testosterone, 5α- and 5β-dihydrotestosterone (-DHT) induce an acute in vitro vasorelaxation and in vivo vasodepressor, hypotensive and antihypertensive responses. Our aim was to study whether androgen-induced blood pressure (BP) reduction is involved with a blockade of Ca2+ influx through L-type voltage-operated calcium channels (L-VOCCs) and/or the signaling pathways of α1 -adrenoceptors to induce vasoconstriction, which are one of the major mechanisms of BP maintenance...
March 12, 2018: Endocrine Research
Timo Gutermuth, Sarah Herbell, Roman Lassig, Mikael Brosché, Tina Romeis, José Alberto Feijó, Rainer Hedrich, Kai Robert Konrad
Pollen tubes (PTs) are characterized by having tip-focused cytosolic calcium ion (Ca2+ ) concentration ([Ca2+ ]cyt ) gradients, which are believed to control PT growth. However, the mechanisms by which the apical [Ca2+ ]cyt orchestrates PT growth are not well understood. Here, we aimed to identify these mechanisms by combining reverse genetics, cell biology, electrophysiology, and live-cell Ca2+ and anion imaging. We triggered Ca2+ -channel activation by applying hyperpolarizing voltage pulses and observed that the evoked [Ca2+ ]cyt increases were paralleled by high anion channel activity and a decrease in the cytosolic anion concentration at the PT tip...
March 9, 2018: New Phytologist
Minglin Pan, Ying Han, Aninda Basu, Anzhi Dai, Rui Si, Conor Willson, Angela Balistrieri, Brian T Scott, Ayako Makino
Coronary microvascular rarefaction due to endothelial cell (EC) dysfunction is one of the causes of increased morbidity and mortality in diabetes. Coronary ECs in diabetes are more apoptotic due partly to mitochondrial calcium overload. This study was designed to investigate the role of hexokinase 2 (HK2, an endogenous inhibitor of voltage-dependent anion channel) in coronary endothelial dysfunction in type 2 diabetes. We used mouse coronary ECs (MCECs) isolated from type 2 diabetic mice and human coronary ECs (HCECs) from type 2 diabetic patients to examine protein levels and mitochondrial functions...
March 7, 2018: American Journal of Physiology. Cell Physiology
Prosper N'Gouemo
Voltage-sensitive Ca2+ (CaV ) channels are the primary route of depolarization-induced Ca2+ entry in neurons and other excitable cells, leading to an increase in intracellular Ca2+ concentration ([Ca2+ ]i ). The resulting increase in [Ca2+ ]i activates a wide range of Ca2+ -dependent processes in neurons, including neurotransmitter release, gene transcription, activation of Ca2+ -dependent enzymes, and activation of certain K+ channels and chloride channels. In addition to their key roles under physiological conditions, CaV channels are also an important target of alcohol, and alcohol-induced changes in Ca2+ signaling can disturb neuronal homeostasis, Ca2+ -mediated gene transcription, and the function of neuronal circuits, leading to various neurological and/or neuropsychiatric symptoms and disorders, including alcohol withdrawal induced-seizures and alcoholism...
March 3, 2018: Handbook of Experimental Pharmacology
Noriyuki Hatano, Susumu Ohya, Yuji Imaizumi, Robert B Clark, Darrell Belke, Wayne R Giles
KEY POINTS: Fibroblasts isolated from adult rat ventricles consistently respond to (5-100 μM) ATP. ATP, ADP, and UTP all elicit similar dose-dependent increases in [Ca2+ ]i . ATP also activates an outwardly rectifying Cl- current; in contrast, ADP and UTP have much smaller electrophysiological effects. This ATP-dependent Cl- current is markedly reduced when: i) [Ca2+ ]i is buffered with BAPTA, or ii) the intrinsic phospholipase C activity in these fibroblasts is inhibited. PCR analysis suggests that the ATP-induced current is generated by the Ca2+ -activated Cl- current transcript TMEM 16F, also denoted ANO6...
March 1, 2018: Experimental Physiology
Tobias Atkin, Stefano Comai, Gabriella Gobbi
Although the GABAergic benzodiazepines (BZDs) and Z-drugs (zolpidem, zopiclone, and zaleplon) are FDA-approved for insomnia disorders with a strong evidence base, they have many side effects, including cognitive impairment, tolerance, rebound insomnia upon discontinuation, car accidents/falls, abuse, and dependence liability. Consequently, the clinical use of off-label drugs and novel drugs that do not target the GABAergic system is increasing. The purpose of this review is to analyze the neurobiological and clinical evidence of pharmacological treatments of insomnia, excluding the BZDs and Z-drugs...
April 2018: Pharmacological Reviews
Armando Carpaneto, Antonella Gradogna
Plant two-pore channels (TPCs) are non-selective cation channels permeable both to monovalent potassium and divalent calcium. We previously developed a technique that allowed the simultaneous determination of the fluxes of these two ions across the channel by a combined use of patch-clamp and fluorescence. In this paper we studied how potassium and calcium fluxes were influenced by modification of cytosolic concentrations of K+ and Ca2+ . A decrease in cytosolic calcium from 2 to 0.5 mM led to a shift of the activation curve of about +60 mV; although at positive potentials currents were very similar, calcium ion permeation was significantly reduced and the ratio between the total and calcium-mediated current increased about two-fold...
February 24, 2018: Biophysical Chemistry
Mena Abdelsayed, Manpreet Ruprai, Peter C Ruben
E1784K is the most common mixed syndrome SCN5a mutation underpinning both Brugada syndrome type 1 (BrS1) and Long-QT syndrome type 3 (LQT3). The charge reversal mutant enhances the late sodium current (INa ) passed by the cardiac voltage-gated sodium channel (NaV 1.5), delaying cardiac repolarization. Exercise-induced triggers, like elevated temperature and cytosolic calcium, exacerbate E1784K late INa . In this study, we tested the effects of Ranolazine, the late INa blocker, on voltage-dependent and kinetic properties of E1784K at elevated temperature and cytosolic calcium...
February 26, 2018: Scientific Reports
Christian J Peters, John M Gilchrist, Jason Tien, Neville P Bethel, Lijun Qi, Tingxu Chen, Lynn Wang, Yuh Nung Jan, Michael Grabe, Lily Y Jan
Calcium-activated chloride channels (CaCCs) formed by TMEM16A or TMEM16B are broadly expressed in the nervous system, smooth muscles, exocrine glands, and other tissues. With two calcium-binding sites and a pore within each monomer, the dimeric CaCC exhibits voltage-dependent calcium sensitivity. Channel activity also depends on the identity of permeant anions. To understand how CaCC regulates neuronal signaling and how CaCC is, in turn, modulated by neuronal activity, we examined the molecular basis of CaCC gating...
February 16, 2018: Neuron
Ana Laura Sanchez-Sandoval, Zazil Herrera Carrillo, Clara Estela Díaz Velásquez, Dulce María Delgadillo, Heriberto Manuel Rivera, Juan Carlos Gomora
Voltage-gated calcium channels contain four highly conserved transmembrane helices known as S4 segments that exhibit a positively charged residue every third position, and play the role of voltage sensing. Nonetheless, the activation range between high-voltage (HVA) and low-voltage (LVA) activated calcium channels is around 30-40 mV apart, despite the high level of amino acid similarity within their S4 segments. To investigate the contribution of S4 voltage sensors for the low-voltage activation characteristics of CaV3...
2018: PloS One
Jens Ingwersen, Lorenzo De Santi, Britta Wingerath, Jonas Graf, Barbara Koop, Reiner Schneider, Christina Hecker, Friederike Schröter, Mary Bayer, Anna Dorothee Engelke, Michael Dietrich, Philipp Albrecht, Hans-Peter Hartung, Pasquale Annunziata, Orhan Aktas, Tim Prozorovski
Multiple sclerosis (MS) is characterized by inflammatory neurodegeneration, with axonal injury and neuronal cell death occurring in parallel to demyelination. Regarding the molecular mechanisms responsible for demyelination and axonopathy, energy failure, aberrant expression of ion channels and excitotoxicity have been suggested to lead to Ca2+ overload and subsequent activation of calcium-dependent damage pathways. Thus, the inhibition of Ca2+ influx by pharmacological modulation of Ca2+ channels may represent a novel neuroprotective strategy in the treatment of secondary axonopathy...
February 23, 2018: Journal of Neurochemistry
Mónica Rubio Ayala, Tatiana Syrovets, Susanne Hafner, Vitalii Zablotskii, Alexandr Dejneka, Thomas Simmet
Cellular function is modulated by the electric membrane potential controlling intracellular physiology and signal propagation from a motor neuron to a muscle fiber resulting in muscle contraction. Unlike electric fields, magnetic fields are not attenuated by biological materials and penetrate deep into the tissue. We used complex spatiotemporal magnetic fields (17-70 mT) to control intracellular signaling in skeletal muscle cells. By changing different parameters of the alternating magnetic field (amplitude, inversion time, rotation frequency), we induced transient depolarization of cellular membranes leading to i) Na+ influx through voltage-gated sodium channels (VGSC), ii) cytosolic calcium increase, and iii) VGSC- and ryanodine receptor-dependent increase of actin polymerization...
February 16, 2018: Biomaterials
Tamara Timic Stamenic, Slobodan M Todorovic
The central medial nucleus (CeM) is a part of the intralaminar thalamus, which is involved in the control of arousal and sensory processing. However, ionic conductances and mechanisms that regulate the activity of the CeM are not well studied. Here, we used in vitro electrophysiology in acute brain slices from adolescent rats to demonstrate that T-type calcium currents (T-currents) are prominent in the majority of the studied CeM neurons and are critical determinants of low-threshold calcium spikes (LTSs), which in turn regulate excitability of these neurons...
January 2018: ENeuro
Hirotake Ishida, Shin-Ya Saito, Eita Hishinuma, Tomoaki Kitayama, Tomohisa Ishikawa
Our previous studies have shown that α1 -adrenoceptors, in addition to α2 -adrenoceptors, are involved in enhanced contraction of cutaneous blood vessels during cooling. The present study aimed to elucidate the mechanism underlying it. In tail and iliac arteries isolated from rats, isometric contraction was measured using a myograph and the phosphorylation level of myosin phosphatase target subunit 1 (MYPT1) was quantified by western blotting. The phenylephrine-induced contraction was enhanced by cooling to 24°C in tail arteries, but was suppressed in iliac arteries...
February 16, 2018: European Journal of Pharmacology
Yan Yang, Yihui Cui, Kangning Sang, Yiyan Dong, Zheyi Ni, Shuangshuang Ma, Hailan Hu
The N-methyl-d-aspartate receptor (NMDAR) antagonist ketamine has attracted enormous interest in mental health research owing to its rapid antidepressant actions, but its mechanism of action has remained elusive. Here we show that blockade of NMDAR-dependent bursting activity in the 'anti-reward center', the lateral habenula (LHb), mediates the rapid antidepressant actions of ketamine in rat and mouse models of depression. LHb neurons show a significant increase in burst activity and theta-band synchronization in depressive-like animals, which is reversed by ketamine...
February 14, 2018: Nature
Jiangyong Yu, Shuhang Wang, Wei Zhao, Jianchun Duan, Zhijie Wang, Hanxiao Chen, Yanhua Tian, Di Wang, Jun Zhao, Tongtong An, Hua Bai, Meina Wu, Jie Wang
PURPOSE: Chemo-resistance in small cell lung cancer (SCLC) is reportedly attributed to the existence of resistant cancer stem cells (CSCs). Studies involving CSC-specific markers and related mechanisms in SCLC remain limited. The current study explored the role of the voltage-dependent calcium channel α2δ1 subunit as a CSC marker in chemo-resistant SCLC, and explored the potential mechanisms of α2δ1-mediated chemo-resistance and strategies of overcoming the resistance. EXPERIMENTAL DESIGN: α2δ1 positive cells were identified and isolated from SCLC cell lines and patient derived xenografts (PDXs) models, and CSC-like properties were subsequently verified...
February 6, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Aram Chang, Fayal Abderemane-Ali, Greg L Hura, Nathan D Rossen, Rachel E Gate, Daniel L Minor
Kv7 (KCNQ) voltage-gated potassium channels control excitability in the brain, heart, and ear. Calmodulin (CaM) is crucial for Kv7 function, but how this calcium sensor affects activity has remained unclear. Here, we present X-ray crystallographic analysis of CaM:Kv7.4 and CaM:Kv7.5 AB domain complexes that reveal an Apo/CaM clamp conformation and calcium binding preferences. These structures, combined with small-angle X-ray scattering, biochemical, and functional studies, establish a regulatory mechanism for Kv7 CaM modulation based on a common architecture in which a CaM C-lobe calcium-dependent switch releases a shared Apo/CaM clamp conformation...
February 21, 2018: Neuron
Alpana Singh, Poonam Verma, Anu Raju, Kochupurackal P Mohanakumar
We have recently demonstrated neuroprotective abilities of nimodipine, an L-type voltage dependent calcium channel (VDCC) blocker in cellular and animal models of Parkinson's disease (PD). To understand the calcium regulatory mechanisms in the disease pathogenesis, the present study examined calcium regulatory proteins calbindin and calpain mRNA and protein levels employing quantitative PCR and western blot in 1-methyl-4-phenyl pyridinium ion (MPP+)-treated SH-SY5Y cell lines and in the striatum of mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)...
February 7, 2018: Journal of Chemical Neuroanatomy
Jie Hua Xu, Hui Wang, Wen Zhang, Feng Ru Tang
Voltage-dependent calcium channels (VDCC) have been shown to regulate neuronal excitability and their antagonists have been used clinically for the control of seizures. While functional studies of VDCC in epileptogenesis in the CA1 area of hippocampus or the dentate gyrus have been done, few studies were carried out in the CA3 area. Given the bursting characteristics of the CA3 neurons, we speculated that VDCC in the CA3 area might play an important role in the epileptogenesis. In the present study in the mouse pilocarpine model of temporal lobe epilepsy, we investigated the alterations of alpha 1 subunits of L-type VDCC in the CA3 area of the hippocampus at different stages of epileptogenesis, i...
February 7, 2018: Neurochemistry International
Pablo Mendez, Thomas Stefanelli, Carmen E Flores, Dominique Muller, Christian Lüscher
Correlated activity in the hippocampus drives synaptic plasticity that is necessary for the recruitment of neuronal ensembles underlying fear memory. Sustained neural activity, on the other hand, may trigger homeostatic adaptations. However, whether homeostatic plasticity affects memory function remains unknown. Here, we use optogenetics to induce cell autonomous homeostatic plasticity in CA1 pyramidal neurons and granule cells of the hippocampus. High-frequency spike trains applied for 10 min decreased the number of excitatory spine synapses and increased the number of inhibitory shaft synapses...
February 6, 2018: Cell Reports
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