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L-type of voltage-gated Ca2+ channel

Jing-Ying Pan, Shijin Yuan, Tao Yu, Cong-Lin Su, Xiao-Long Liu, Jun He, He Li
Huntingtin associated protein 1 (Hap1) was originally identified as a protein that binds to the Huntington disease protein, huntingtin. Growing evidence has shown that Hap1 participates in intracellular trafficking via its association with various microtubule- dependent transporters and organelles. Recent studies also revealed that Hap1 is involved in exocytosis such as insulin release from pancreatic beta cells.However, the mechanism underlying the action of Hap1 on insulin release remains to be investigated...
September 13, 2016: Journal of Biological Chemistry
Jessica R Thomas, Amy Lee
Voltage-gated Ca(2+) (Cav) channels regulate a variety of biological processes, such as muscle contraction, gene expression, and neurotransmitter release. Cav channels are subject to diverse forms of regulation, including those involving the Ca(2+) ions that permeate the pore. High voltage-activated Cav channels undergo Ca(2+)-dependent inactivation (CDI) and facilitation (CDF), which can regulate processes such as cardiac rhythm and synaptic plasticity. CDI and CDF differ slightly between Cav1 (L-type) and Cav2 (P/Q-, N-, and R-type) channels...
2016: Cold Spring Harbor Protocols
Yoon Kyung Choi, Ji-Hee Kim, Dong-Keon Lee, Kwang-Soon Lee, Moo-Ho Won, Dooil Jeoung, Hansoo Lee, Kwon-Soo Ha, Young-Guen Kwon, Young-Myeong Kim
AIMS: The heme oxygenase-1 (HO-1)/carbon monoxide (CO) pathway induced in astrocytes after ischemic brain injury promotes vascular endothelial growth factor (VEGF) expression to maintain and repair neurovascular function. Although HO-1-derived CO has been shown to induce hypoxia-inducible factor-1α (HIF-1α)-dependent VEGF expression, the underlying mechanism independent of HIF-1α remains to be elucidated. RESULTS: HO-1 and VEGF were co-expressed in astrocytes of ischemic mouse brain tissues...
August 23, 2016: Antioxidants & Redox Signaling
David Weise, Jakob Mann, Jost-Julian Rumpf, Stefan Hallermann, Joseph Classen
Activity-dependent changes of postsynaptic Ca(2+)-concentration are influenced by a variety of different Ca(2+)-channels and play an important role in synaptic plasticity. Paired associative stimulation (PAS) and theta-burst stimulation (TBS) are noninvasive magnetic stimulation protocols used in human subjects to induce lasting corticospinal excitability changes that have been likened to synaptic long-term potentiation and long-term depression. To better characterize the Ca(2+)-related physiological mechanisms underlying PAS- and TBS-induced plasticity, we examined the impact of different Ca(2+)-sources...
July 11, 2016: Cerebral Cortex
Dongyang Huang, Sha Huang, Haixia Gao, Yani Liu, Jinlong Qi, Pingping Chen, Caixue Wang, Jason L Scragg, Alexander Vakurov, Chris Peers, Xiaona Du, Hailin Zhang, Nikita Gamper
AIMS: Neuropeptide substance P (SP) is produced and released by a subset of peripheral sensory neurons that respond to tissue damage (nociceptors). SP exerts excitatory effects in the central nervous system, but peripheral SP actions are still poorly understood; therefore, here, we aimed at investigating these peripheral mechanisms. RESULTS: SP acutely inhibited T-type voltage-gated Ca(2+) channels in nociceptors. The effect was mediated by neurokinin 1 (NK1) receptor-induced stimulation of intracellular release of reactive oxygen species (ROS), as it can be prevented or reversed by the reducing agent dithiothreitol and mimicked by exogenous or endogenous ROS...
August 10, 2016: Antioxidants & Redox Signaling
Christian Schön, François Paquet-Durand, Stylianos Michalakis
Retinitis pigmentosa is an inherited blinding disorder characterized by progressive degeneration and loss of photoreceptors. The exact mechanism of degeneration and cell death of photoreceptors is not known, but is thought to involve disturbed Ca2+-signaling. Ca2+ can enter the photoreceptor cell via outer segment cyclic nucleotide-gated (CNG) channels or synaptic Cav1.4 L-type voltage-gated calcium channels (VGCC). Previously, we have shown that genetic ablation of the Cngb1 gene encoding the B subunit of the rod CNG channel delays the fast progressing degeneration in the rd1 mutant mouse model of retinitis pigmentosa...
2016: PloS One
Mark D Levin, Gautam K Singh, Hai Xia Zhang, Keita Uchida, Beth A Kozel, Phyllis K Stein, Atilla Kovacs, Ruth E Westenbroek, William A Catterall, Dorothy Katherine Grange, Colin G Nichols
Cantu syndrome (CS) is caused by gain-of-function (GOF) mutations in genes encoding pore-forming (Kir6.1, KCNJ8) and accessory (SUR2, ABCC9) KATP channel subunits. We show that patients with CS, as well as mice with constitutive (cGOF) or tamoxifen-induced (icGOF) cardiac-specific Kir6.1 GOF subunit expression, have enlarged hearts, with increased ejection fraction and increased contractility. Whole-cell voltage-clamp recordings from cGOF or icGOF ventricular myocytes (VM) show increased basal L-type Ca(2+) current (LTCC), comparable to that seen in WT VM treated with isoproterenol...
June 14, 2016: Proceedings of the National Academy of Sciences of the United States of America
Thom Griffith, Krasimira Tsaneva-Atanasova, Jack R Mellor
The key trigger for Hebbian synaptic plasticity is influx of Ca2+ into postsynaptic dendritic spines. The magnitude of [Ca2+] increase caused by NMDA-receptor (NMDAR) and voltage-gated Ca2+ -channel (VGCC) activation is thought to determine both the amplitude and direction of synaptic plasticity by differential activation of Ca2+ -sensitive enzymes such as calmodulin. Ca2+ influx is negatively regulated by Ca2+ -activated K+ channels (SK-channels) which are in turn inhibited by neuromodulators such as acetylcholine...
May 2016: PLoS Computational Biology
Bin Pan, Yuan Guo, Hsiang-En Wu, John Park, Van Nancy Trinh, Z David Luo, Quinn H Hogan
Loss of high-voltage-activated (HVA) calcium current (ICa) and gain of low-voltage-activated (LVA) ICa after painful peripheral nerve injury cause elevated excitability in sensory neurons. Nerve injury is also accompanied by increased expression of the extracellular matrix glycoprotein thrombospondin-4 (TSP4), and interruption of TSP4 function can reverse or prevent behavioral hypersensitivity after injury. We therefore investigated TSP4 regulation of ICa in dorsal root ganglion (DRG) neurons. During depolarization adequate to activate HVA ICa, TSP4 decreases both N- and L-type ICa and the associated intracellular calcium transient...
September 2016: Pain
Li Xie, Subhankar Dolai, Youhou Kang, Tao Liang, Huanli Xie, Tairan Qin, Lu Yang, Liangyi Chen, Herbert Y Gaisano
Syntaxin (Syn)-1A mediates exocytosis of predocked insulin-containing secretory granules (SGs) during first-phase glucose-stimulated insulin secretion (GSIS) in part via its interaction with plasma membrane (PM)-bound L-type voltage-gated calcium channels (Cav). In contrast, Syn-3 mediates exocytosis of newcomer SGs that accounts for second-phase GSIS. We now hypothesize that the newcomer SG Syn-3 preferentially binds and modulates R-type Cav opening, which was postulated to mediate second-phase GSIS. Indeed, glucose-stimulation of pancreatic islet β-cell line INS-1 induced a predominant increase in interaction between Syn-3 and Cavα1 pore-forming subunits of R-type Cav2...
2016: PloS One
Juliane Brun, Katrin A Lutz, Katharina M H Neumayer, Gerd Klein, Tanja Seeger, Tatiana Uynuk-Ool, Katharina Wörgötter, Sandra Schmid, Udo Kraushaar, Elke Guenther, Bernd Rolauffs, Wilhelm K Aicher, Melanie L Hart
The use of mesenchymal stromal cells (MSCs) differentiated toward a smooth muscle cell (SMC) phenotype may provide an alternative for investigators interested in regenerating urinary tract organs such as the bladder where autologous smooth muscle cells cannot be used or are unavailable. In this study we measured the effects of good manufacturing practice (GMP)-compliant expansion followed by myogenic differentiation of human MSCs on the expression of a range of contractile (from early to late) myogenic markers in relation to the electrophysiological parameters to assess the functional role of the differentiated MSCs and found that differentiation of MSCs associated with electrophysiological competence comparable to bladder SMCs...
2015: PloS One
Aaron Provence, Kiril L Hristov, Shankar P Parajuli, Georgi V Petkov
Estrogen replacement therapies have been suggested to be beneficial in alleviating symptoms of overactive bladder. However, the precise regulatory mechanisms of estrogen in urinary bladder smooth muscle (UBSM) at the cellular level remain unknown. Large conductance voltage- and Ca2+-activated K+ (BK) channels, which are key regulators of UBSM function, are suggested to be non-genomic targets of estrogens. This study provides an electrophysiological investigation into the role of UBSM BK channels as direct targets for 17β-estradiol, the principle estrogen in human circulation...
2015: PloS One
Hengtao Zhang, Albert Y Sun, Jong J Kim, Victoria Graham, Elizabeth A Finch, Igor Nepliouev, Guiling Zhao, Tianyu Li, W J Lederer, Jonathan A Stiber, Geoffrey S Pitt, Nenad Bursac, Paul B Rosenberg
Cardiac pacemaking is governed by specialized cardiomyocytes located in the sinoatrial node (SAN). SAN cells (SANCs) integrate voltage-gated currents from channels on the membrane surface (membrane clock) with rhythmic Ca(2+) release from internal Ca(2+) stores (Ca(2+) clock) to adjust heart rate to meet hemodynamic demand. Here, we report that stromal interaction molecule 1 (STIM1) and Orai1 channels, key components of store-operated Ca(2+) entry, are selectively expressed in SANCs. Cardiac-specific deletion of STIM1 in mice resulted in depletion of sarcoplasmic reticulum (SR) Ca(2+) stores of SANCs and led to SAN dysfunction, as was evident by a reduction in heart rate, sinus arrest, and an exaggerated autonomic response to cholinergic signaling...
October 13, 2015: Proceedings of the National Academy of Sciences of the United States of America
Christina Poetschke, Elena Dragicevic, Johanna Duda, Julia Benkert, Antonios Dougalis, Roberta DeZio, Terrance P Snutch, Joerg Striessnig, Birgit Liss
The preferential degeneration of Substantia nigra dopamine midbrain neurons (SN DA) causes the motor-symptoms of Parkinson's disease (PD). Voltage-gated L-type calcium channels (LTCCs), especially the Cav1.3-subtype, generate an activity-related oscillatory Ca(2+) burden in SN DA neurons, contributing to their degeneration and PD. While LTCC-blockers are already in clinical trials as PD-therapy, age-dependent functional roles of Cav1.3 LTCCs in SN DA neurons remain unclear. Thus, we analysed juvenile and adult Cav1...
September 18, 2015: Scientific Reports
José A Fernández, Mary K McGahon, J Graham McGeown, Tim M Curtis
PURPOSE: Although L-type Ca2+ channels are known to play a key role in the myogenic reactivity of retinal arterial vessels, the involvement of other types of voltage-gated Ca2+ channels in this process remains unknown. In the present study we have investigated the contribution of T-type Ca2+ channels to myogenic signaling in arterioles of the rat retinal microcirculation. METHODS: Confocal immunolabeling of whole-mount preparations was used to investigate the localization of CaV3...
August 2015: Investigative Ophthalmology & Visual Science
Iulia Glovaci, C Andrew Chapman
The lateral entorhinal cortex receives strong inputs from midbrain dopamine neurons that can modulate its sensory and mnemonic function. We have previously demonstrated that 1 µM dopamine facilitates synaptic transmission in layer II entorhinal cortex cells via activation of D1-like receptors, increased cAMP-PKA activity, and a resulting enhancement of AMPA-receptor mediated currents. The present study assessed the contribution of phosphatidylinositol (PI)-linked D1 receptors to the dopaminergic facilitation of transmission in layer II of the rat entorhinal cortex, and the involvement of phospholipase C activity and release of calcium from internal stores...
2015: PloS One
Shi-xing Wu, Li Yang, Xiao-qiang Lu
OBJECTIVE: To study whether the analgesis of oxymatrine (OMT) affects N-type voltage-gated calcium channels (VGCCs). METHODS: Totally 45 mice were randomly divided into the sham-operation group, the model group [established by partial sciatic nerve ligation (PSNL)] , and the OMT treatment group according to random digit table, 15 in each group. The dorsal root ganglions (DRG) were separated in PSNL pain model mice. Intracellular calcium concentration ([Ca2+]i) was determined with Fluo-3 AM immunofluorescent probe in cultured DRG neurons...
April 2015: Chinese Journal of Integrated Traditional and Western Medicine
Sangyong Jung, Tomoko Oshima-Takago, Rituparna Chakrabarti, Aaron B Wong, Zhizi Jing, Gulnara Yamanbaeva, Maria Magdalena Picher, Sonja M Wojcik, Fabian Göttfert, Friederike Predoehl, Katrin Michel, Stefan W Hell, Susanne Schoch, Nicola Strenzke, Carolin Wichmann, Tobias Moser
Ca(2+) influx triggers the fusion of synaptic vesicles at the presynaptic active zone (AZ). Here we demonstrate a role of Ras-related in brain 3 (Rab3)-interacting molecules 2α and β (RIM2α and RIM2β) in clustering voltage-gated CaV1.3 Ca(2+) channels at the AZs of sensory inner hair cells (IHCs). We show that IHCs of hearing mice express mainly RIM2α, but also RIM2β and RIM3γ, which all localize to the AZs, as shown by immunofluorescence microscopy. Immunohistochemistry, patch-clamp, fluctuation analysis, and confocal Ca(2+) imaging demonstrate that AZs of RIM2α-deficient IHCs cluster fewer synaptic CaV1...
June 16, 2015: Proceedings of the National Academy of Sciences of the United States of America
Martin L Pall
This review considers a paradigm shift on microwave electromagnetic field (EMF) action from only thermal effects to action via voltage-gated calcium channel (VGCC) activation. Microwave/lower frequency EMFs were shown in two dozen studies to act via VGCC activation because all effects studied were blocked by calcium channel blockers. This mode of action was further supported by hundreds of studies showing microwave changes in calcium fluxes and intracellular calcium [Ca2+]i signaling. The biophysical properties of VGCCs/similar channels make them particularly sensitive to low intensity, non-thermal EMF exposures...
2015: Reviews on Environmental Health
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
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