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Nifedipine cav1

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https://www.readbyqxmd.com/read/28193694/different-cav1-3-channel-isoforms-control-distinct-components-of-the-synaptic-vesicle-cycle-in-auditory-inner-hair-cells
#1
Philippe Fy Vincent, Yohan Bouleau, Gilles Charpentier, Alice Emptoz, Saaid Safieddine, Christine Petit, Didier Dulon
The mechanisms orchestrating transient and sustained exocytosis in auditory inner hair cells (IHCs) remain largely unknown. These exocytotic responses are believed to mobilize sequentially a readily releasable pool of vesicles (RRP) underneath the synaptic ribbons and a slowly releasable pool of vesicles (SRP) at farther distance from them. They are both governed by Cav1.3 channels and require otoferlin as Ca(2+) sensor but whether they use the same Cav1.3 isoforms is still unknown. Using whole cell patch clamp recordings in post-hearing mice, we show that only a proportion (∼25 %) of the total Ca(2+) current in IHCs, displaying fast inactivation and resistance to 20 μM nifedipine, a L-type Ca(2+) channel blocker, is sufficient to trigger RRP but not SRP exocytosis...
February 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28185965/cav1-2-but-not-cav1-3-l-type-calcium-channel-subtype-mediates-nicotine-induced-conditioned-place-preference-in-miceo
#2
Yudan Liu, Meghan Harding, Jules Dore, Xihua Chen
Nicotine use is one of the most common forms of drug addiction. Although L-type calcium channels (LTCCs) are involved in nicotine addiction, the contribution of the two primary LTCC subtypes (Cav1.2 and 1.3) is unknown. This study aims to determine the contribution of these two LTCC subtypes to nicotine-induced conditioned place preference (CPP) responses by using transgenic mouse models that do not express Cav1.3 (Cav1.3(-/-)) or contain a mutation in the dihydropyridine (DHP) site of the Cav1.2 (Cav1.2DHP(-/-))...
February 6, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28026020/low-pho-boosts-burst-firing-and-catecholamine-release-by-blocking-task-1-and-bk-channels-while-preserving-cav1-channels-in-mouse-chromaffin-cells
#3
Laura Guarina, David H F Vandael, Valentina Carabelli, Emilio Carbone
Mouse chromaffin cells (MCCs) generate action potential (AP) firing that regulates the Ca(2+) -dependent release of catecholamines (CAs). Recent findings indicate that MCCs possess a variety of spontaneous firing modes that span from the common "tonic-irregular" to the less frequent "burst" firing. This latter is evident in a small fraction of MCCs but occurs regularly when Nav1.3/1.7 channels are made less available or when the Slo1β2-subunit responsible for BK channel inactivation is deleted. Burst firing causes massive increases of Ca(2+) -entry and potentiates CA release ∼3...
December 27, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27988286/human-native-cav1-channels-in-chromaffin-cells-contribution-to-exocytosis-and-firing-of-spontaneous-action-potentials
#4
Alicia Hernández-Vivanco, Sara Sanz-Lázaro, Amanda Jiménez-Pompa, Nuria García-Magro, Beatriz Carmona-Hidalgo, Alberto Pérez-Alvarez, Jose Carlos Caba-González, Angel Tabernero, Sergio Alonso Y Gregorio, Juan Passas, Jesús Blázquez, Carmen González-Enguita, Cristina de Castro-Guerín, Almudena Albillos
The present study was performed to evaluate the Cav1 channel subtypes expressed in human chromaffin cells and the role that these channels play in exocytosis and cell excitability. Here we show that human chromaffin cells obtained from organ donors express Cav1.2 and Cav1.3 subtypes using molecular and pharmacological techniques. Immunocytochemical data demonstrated the presence of Cav1.2 and Cav1.3 subtypes, but not Cav1.1 or Cav1.4. Electrophysiological experiments were conducted to investigate the contribution of Cav1 channels to the exocytotic process and cell excitability...
December 14, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27520758/interaction-between-amiodarone-and-hepatitis-c-virus-nucleotide-inhibitors-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-and-hek-293-cav1-2-over-expressing-cells
#5
Armando Lagrutta, Haoyu Zeng, John Imredy, Bharathi Balasubramanian, Spencer Dech, Edward Lis, Jixin Wang, Jin Zhai, Joseph DeGeorge, Frederick Sannajust
Several clinical cases of severe bradyarrhythmias have been reported upon co-administration of the Hepatitis-C NS5B Nucleotide Polymerase Inhibitor (HCV-NI) direct-acting antiviral agent, sofosbuvir (SOF), and the Class-III anti-arrhythmic amiodarone (AMIO). We model the cardiac drug-drug interaction (DDI) between AMIO and SOF, and between AMIO and a closely-related SOF analog, MNI-1 (Merck Nucleotide Inhibitor #1), in functional assays of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), to provide mechanistic insights into recently reported clinical cases...
October 1, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27242545/aging-reduces-l-type-calcium-channel-current-and-the-vasodilatory-response-of-small-mesenteric-arteries-to-calcium-channel-blockers
#6
Sulayma A Albarwani, Fathi Mansour, Abdul Aleem Khan, Intisar Al-Lawati, Abdulla Al-Kaabi, Al-Manar Al-Busaidi, Safa Al-Hadhrami, Isehaq Al-Husseini, Sultan Al-Siyabi, Musbah O Tanira
Calcium channel blockers (CCBs) are widely used to treat cardiovascular disease (CVD) including hypertension. As aging is an independent risk factor for CVD, the use of CCBs increases with increasing age. Hence, this study was designed to evaluate the effect of aging on the sensitivity of small mesenteric arteries to L-type voltage-gated calcium channel (LTCC) blockers and also to investigate whether there was a concomitant change in calcium current density. Third order mesenteric arteries from male F344 rats, aged 2...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27114559/gdf-15-enhances-intracellular-ca2-by-increasing-cav1-3-expression-in-rat-cerebellar-granule-neurons
#7
Jun-Mei Lu, Chang-Ying Wang, Changlong Hu, Yan-Jia Fang, Yan-Ai Mei
GDF-15 (growth/differentiation factor 15) is a novel member of the TGF (transforming growth factor)-β superfamily that has critical roles in the central and peripheral nervous systems. We reported previously that GDF-15 increased delayed rectifier outward K(+) currents and Kv2.1 α subunit expression through TβRII (TGF-β receptor II) to activate Src kinase and Akt/mTOR (mammalian target of rapamycin) signalling in rat CGNs (cerebellar granule neurons). In the present study, we found that treatment of CGNs with GDF-15 for 24 h increased the intracellular Ca(2+) concentration ([Ca(2+)]i) in response to membrane depolarization, as determined by Ca(2+) imaging...
July 1, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27108787/na-permeates-through-l-type-ca-2-channel-in-bovine-airway-smooth-muscle
#8
Bettina Sommer, Edgar Flores-Soto, Jorge Reyes-García, Verónica Díaz-Hernández, Verónica Carbajal, Luis M Montaño
UNLABELLED: Membrane depolarization of airway smooth muscle (ASM) opens L-type voltage dependent Ca(2+) channels (L-VDCC) allowing Ca(2+) entrance to produce contraction. In Ca(2+) free conditions Na(+) permeates through L-VDCC in excitable and non-excitable cells and this phenomenon is annulled at µM Ca(2+) concentrations. Membrane depolarization also induces activation of Gq proteins and sarcoplasmic reticulum Ca(2+) release. In bovine ASM, KCl induced a transient contraction sensitive to nifedipine in Ca(2+)free medium, indicating an additional mechanism to the SR-Ca(2+) release...
July 5, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27098837/regulation-of-aldosterone-secretion-by-cav1-3
#9
Catherine B Xie, Lalarukh Haris Shaikh, Sumedha Garg, Gizem Tanriver, Ada E D Teo, Junhua Zhou, Carmela Maniero, Wanfeng Zhao, Soosung Kang, Richard B Silverman, Elena A B Azizan, Morris J Brown
Aldosterone-producing adenomas (APAs) vary in phenotype and genotype. Zona glomerulosa (ZG)-like APAs frequently have mutations of an L-type calcium channel (LTCC) CaV1.3. Using a novel antagonist of CaV1.3, compound 8, we investigated the role of CaV1.3 on steroidogenesis in the human adrenocortical cell line, H295R, and in primary human adrenal cells. This investigational drug was compared with the common antihypertensive drug nifedipine, which has 4.5-fold selectivity for the vascular LTCC, CaV1.2, over CaV1...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27014060/ion-fluxes-through-kca2-sk-and-cav1-l-type-channels-contribute-to-chronoselectivity-of-adenosine-a1-receptor-mediated-actions-in-spontaneously-beating-rat-atria
#10
Bruno Bragança, Nádia Oliveira-Monteiro, Fátima Ferreirinha, Pedro A Lima, Miguel Faria, Ana P Fontes-Sousa, Paulo Correia-de-Sá
Impulse generation in supraventricular tissue is inhibited by adenosine and acetylcholine via the activation of A1 and M2 receptors coupled to inwardly rectifying GIRK/KIR3.1/3.4 channels, respectively. Unlike M2 receptors, bradycardia produced by A1 receptors activation predominates over negative inotropy. Such difference suggests that other ion currents may contribute to adenosine chronoselectivity. In isolated spontaneously beating rat atria, blockade of KCa2/SK channels with apamin and Cav1 (L-type) channels with nifedipine or verapamil, sensitized atria to the negative inotropic action of the A1 agonist, R-PIA, without affecting the nucleoside negative chronotropy...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/26875775/progesterone-suppressed-vasoconstriction-in-human-umbilical-vein-via-reducing-calcium-entry
#11
Yun He, Qinqin Gao, Bing Han, Xiaolin Zhu, Di Zhu, Jianying Tao, Jie Chen, Zhice Xu
The aim of this study was to evaluate the actions of progesterone on human umbilical vein (HUV) from normal pregnancies and the possible underlying mechanisms involved. HUV rings were suspended in organ baths and exposed to progesterone followed by phenylephrine (PE) or serotonin (5-HT). Progesterone suppressed PE- or 5-HT-induced vasoconstriction in HUV rings. The inhibitory effect induced by progesterone was not influenced by nitric oxide syntheses inhibitor, prostaglandins syntheses blocker, the integrity of endothelium, selective progesterone receptor or potassium channel antagonists...
April 2016: Steroids
https://www.readbyqxmd.com/read/26702400/a-role-for-cav1-and-calcineurin-signaling-in-depolarization-induced-changes-in-neuronal-dna-methylation
#12
Eilis Hannon, Annisa N Chand, Mark D Evans, Chloe C Y Wong, Matthew S Grubb, Jonathan Mill
Direct manipulations of neuronal activity have been shown to induce changes in DNA methylation (DNAm), although little is known about the cellular signaling pathways involved. Using reduced representation bisulfite sequencing, we identify DNAm changes associated with moderate chronic depolarization in dissociated rat hippocampal cultures. Consistent with previous findings, these changes occurred primarily in the vicinity of loci implicated in neuronal function, being enriched in intergenic regions and underrepresented in CpG-rich promoter regulatory regions...
July 2015: Neuroepigenetics
https://www.readbyqxmd.com/read/25902901/exercise-intensity-dependent-reverse-and-adverse-remodeling-of-voltage-gated-ca-2-channels-in-mesenteric-arteries-from-spontaneously-hypertensive-rats
#13
Yu Chen, Hanmeng Zhang, Yanyan Zhang, Ni Lu, Lin Zhang, Lijun Shi
Exercise can be regarded as a drug for treating hypertension, and the 'dosage' (intensity/volume) is therefore of great importance. L-type voltage-gated Ca(2+) (Cav1.2) channels on the plasma membrane of vascular smooth muscle cells have a pivotal role in modulating the vascular tone, and the upregulation of Cav1.2 channels is a hallmark feature of hypertension. The present study investigated the beneficial and adverse effects of exercise at different intensities on the remodeling of the Cav1.2 channel in mesenteric arteries (MAs) of spontaneously hypertensive rats (SHRs)...
October 2015: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/25788571/adrenal-fasciculata-cells-express-t-type-and-rapidly-and-slowly-activating-l-type-ca2-channels-that-regulate-cortisol-secretion
#14
John J Enyeart, Judith A Enyeart
In whole cell patch-clamp recordings, we characterized the L-type Ca(2+) currents in bovine adrenal zona fasciculata (AZF) cells and explored their role, along with the role of T-type channels, in ACTH- and angiotensin II (ANG II)-stimulated cortisol secretion. Two distinct dihydropyridine-sensitive L-type currents were identified, both of which were activated at relatively hyperpolarized potentials. One activated with rapid kinetics and, in conjunction with Northern blotting and PCR, was determined to be Cav1...
June 1, 2015: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/25762319/physiological-and-pharmacological-modulation-of-the-embryonic-skeletal-muscle-calcium-channel-splice-variant-cav1-1e
#15
Bruno Benedetti, Petronel Tuluc, Vincenzo Mastrolia, Clemens Dlaska, Bernhard E Flucher
CaV1.1e is the voltage-gated calcium channel splice variant of embryonic skeletal muscle. It differs from the adult CaV1.1a splice variant by the exclusion of exon 29 coding for 19 amino acids in the extracellular loop connecting transmembrane domains IVS3 and IVS4. Like the adult splice variant CaV1.1a, the embryonic CaV1.1e variant functions as voltage sensor in excitation-contraction coupling, but unlike CaV1.1a it also conducts sizable calcium currents. Consequently, physiological or pharmacological modulation of calcium currents may have a greater impact in CaV1...
March 10, 2015: Biophysical Journal
https://www.readbyqxmd.com/read/25712868/homer-proteins-mediate-the-interaction-between-stim1-and-cav1-2-channels
#16
Natalia Dionisio, Tarik Smani, Geoffrey E Woodard, Antonio Castellano, Gines M Salido, Juan A Rosado
STIM1 is a ubiquitous Ca2+ sensor of the intracellular, agonist-sensitive, Ca2+ stores that communicates the filling state of the Ca2+ compartments to plasma membrane store-operated Ca2+ (SOC) channels. STIM1 has been presented as a point of convergence between store-operated and voltage-operated Ca2+ influx, both inducing activation of SOC channels while suppressing Cav1.2 channels. Here we report that Homer proteins play a relevant role in the communication between STIM1 and Cav1.2 channels. HEK-293 cells transiently expressing Cav1...
May 2015: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/25497271/the-l-type-voltage-gated-calcium-channel-modulates-microglial-pro-inflammatory-activity
#17
J F Espinosa-Parrilla, M Martínez-Moreno, X Gasull, N Mahy, M J Rodríguez
Under pathological conditions, microglia, the resident CNS immune cells, become reactive and release pro-inflammatory cytokines and neurotoxic factors. We investigated whether this phenotypic switch includes changes in the expression of the L-type voltage-gated calcium channel (VGCC) in a rat model of N-methyl-D-aspartate-induced hippocampal neurodegeneration. Double immunohistochemistry and confocal microscopy evidenced that activated microglia express the L-type VGCC. We then analyzed whether BV2 microglia express functional L-type VGCC, and investigated the latter's role in microglial cytokine release and phagocytic capacity...
January 2015: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/25440572/chronic-exercise-normalizes-changes-in-cav-1-2-and-kca-1-1-channels-in-mesenteric-arteries-from-spontaneously-hypertensive-rats
#18
Lijun Shi, Hanmeng Zhang, Yu Chen, Yujia Liu, Ni Lu, Tengteng Zhao, Lubo Zhang
BACKGROUND AND PURPOSE: Regular physical activity is an effective non-pharmacological therapy for prevention and control of hypertension. However, the underlying mechanisms are not fully understood. Accumulating evidence shows that the elevated vascular tone in hypertension is a consequence of the 'ion channel remodelling' that occurs during sustained high BP. The present study investigated the effects of aerobic exercise on the electrical remodelling of L-type Ca(2+) (Cav 1.2) and large-conductance Ca(2+) -activated K(+) (KCa 1...
April 2015: British Journal of Pharmacology
https://www.readbyqxmd.com/read/25201340/fluoride-affects-calcium-homeostasis-and-osteogenic-transcription-factor-expressions-through-l-type-calcium-channels-in-osteoblast-cell-line
#19
Xiao-Qin Duan, Zhi-Tao Zhao, Xiu-Yun Zhang, Ying Wang, Huan Wang, Da-Wei Liu, Guang-Sheng Li, Ling Jing
Osteoblast L-type voltage-dependent calcium channels (VDCC) play important roles in maintaining intracellular homeostasis and influencing multiple cellular processes. In particular, they contribute to the activities and functions of osteoblasts (OBs). In order to study how L-type VDCC modulate calcium ion (Ca(2+)) homeostasis and the expression of osteogenic transcription factors in OBs exposed to fluoride, MC3T3-E1 cells were exposed to a gradient of concentrations of fluoride (0, 2.0, 5.0, 10.0 mg/L) in combination with 10 μM nifedipine, a specific inhibitor of VDCC, for 48 h...
December 2014: Biological Trace Element Research
https://www.readbyqxmd.com/read/25172950/human-lymphatic-vessel-contractile-activity-is-inhibited-in-vitro-but-not-in-vivo-by-the-calcium-channel-blocker-nifedipine
#20
RANDOMIZED CONTROLLED TRIAL
Niklas Telinius, Sheyanth Mohanakumar, Jens Majgaard, Sukhan Kim, Hans Pilegaard, Einar Pahle, Jørn Nielsen, Marc de Leval, Christian Aalkjaer, Vibeke Hjortdal, Donna Briggs Boedtkjer
Calcium channel blockers (CCB) are widely prescribed anti-hypertensive agents. The commonest side-effect, peripheral oedema, is attributed to a larger arterial than venous dilatation causing increased fluid filtration. Whether CCB treatment is detrimental to human lymphatic vessel function and thereby exacerbates oedema formation is unknown. We observed that spontaneous lymphatic contractions in isolated human vessels (thoracic duct and mesenteric lymphatics) maintained under isometric conditions were inhibited by therapeutic concentrations (nanomolar) of the CCB nifedipine while higher than therapeutic concentrations of verapamil (micromolar) were necessary to inhibit activity...
November 1, 2014: Journal of Physiology
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