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T-type calcium channel

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https://www.readbyqxmd.com/read/28630432/down-regulation-of-kca2-3-channels-causes-erectile-dysfunction-in-mice
#1
Simon Comerma-Steffensen, Attila Kun, Elise R Hedegaard, Susie Mogensen, Christian Aalkjaer, Ralf Köhler, Birgitte Mønster Christensen, Ulf Simonsen
Modulation of endothelial calcium-activated K(+) channels has been proposed as an approach to restore arterial endothelial cell function in disease. We hypothesized that small-conductance calcium-activated K(+) channels (KCa2.3 or SK3) contributes to erectile function. The research was performed in transgenic mice with overexpression (KCa2.3 (T/T(-Dox))) or down-regulation (KCa2.3 (T/T(+Dox))) of the KCa2.3 channels and wild-type C57BL/6-mice (WT). QPCR revealed that KCa2.3 and KCa1.1 channels were the most abundant in mouse corpus cavernosum...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28614222/next-generation-sequencing-identifies-pathogenic-and-modifier-mutations-in-a-consanguineous-chinese-family-with-hypertrophic-cardiomyopathy
#2
Xinlin Zhang, Jun Xie, Suhui Zhu, Yuhan Chen, Lian Wang, Biao Xu
Hypertrophic cardiomyopathy (HCM) is a highly heterogeneous disease displaying considerable interfamilial and intrafamilial phenotypic variation, including disease severity, age of onset, and disease progression. This poorly understood variance raises the possibility of genetic modifier effects, particularly in MYBPC3-associated HCM.In a large consanguineous Chinese HCM family, we identified 8 members harboring the MYBPC3 c.3624delC (p.Lys1209Serfs) disease-causing mutation, but with very disparate phenotypes...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28611661/discovery-and-development-of-calcium-channel-blockers
#3
REVIEW
Théophile Godfraind
In the mid 1960s, experimental work on molecules under screening as coronary dilators allowed the discovery of the mechanism of calcium entry blockade by drugs later named calcium channel blockers. This paper summarizes scientific research on these small molecules interacting directly with L-type voltage-operated calcium channels. It also reports on experimental approaches translated into understanding of their therapeutic actions. The importance of calcium in muscle contraction was discovered by Sidney Ringer who reported this fact in 1883...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28608537/inhibition-of-human-n-and-t-type-calcium-channels-by-an-ortho-phenoxyanilide-derivative-moniro-1
#4
Jeffrey R McArthur, Leonid Motin, Ellen C Gleeson, Sandro Spiller, Richard J Lewis, Peter J Duggan, Kellie L Tuck, David J Adams
BACKGROUND AND PURPOSE: Voltage-gated calcium channels are involved in peripheral and central nervous system nociception. N-type (Cav 2.2) and T-type (Cav 3.1, Cav 3.2 and Cav 3.3) voltage-gated calcium channels are particularly important in studying and treating pain and epilepsy. EXPERIMENTAL APPROACH: In this study, whole-cell patch clamp electrophysiology was used to assess the potency and mechanism of action of a novel ortho-phenoxylanilide derivative, MONIRO-1, against a panel of voltage-gated calcium channels including Cav 1...
June 13, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28608534/recent-advances-in-the-development-of-t-type-calcium-channel-blockers-for-pain-intervention
#5
REVIEW
Terrance P Snutch, Gerald W Zamponi
Cav3.2 T-type calcium channels are important regulators of pain signals in afferent pain pathway, and their activities are dysregulated during various chronic pain states. Therefore it stands to reason that inhibiting T-type calcium channels in dorsal root ganglion neurons and in the spinal dorsal horn can be targeted for pain relief. This is supported by early pharmacological studies with T-type channel blockers such as ethosuximide, and by analgesic effects of siRNA depletion of Cav3.2 channels. In the past five years, considerable effort has been applied towards identifying novel classes of T-type calcium channel blockers...
June 13, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28596175/calcium-signaling-and-cardiac-arrhythmias
#6
REVIEW
Andrew P Landstrom, Dobromir Dobrev, Xander H T Wehrens
There has been a significant progress in our understanding of the molecular mechanisms by which calcium (Ca(2+)) ions mediate various types of cardiac arrhythmias. A growing list of inherited gene defects can cause potentially lethal cardiac arrhythmia syndromes, including catecholaminergic polymorphic ventricular tachycardia, congenital long QT syndrome, and hypertrophic cardiomyopathy. In addition, acquired deficits of multiple Ca(2+)-handling proteins can contribute to the pathogenesis of arrhythmias in patients with various types of heart disease...
June 9, 2017: Circulation Research
https://www.readbyqxmd.com/read/28580512/comparative-effect-of-calcium-channel-blockers-on-glomerular-function-in-hypertensive-patients-with-diabetes-mellitus
#7
Yayoi Nishida, Yasuo Takahashi, Kotoe Tezuka, Satoshi Takeuchi, Tomohiro Nakayama, Satoshi Asai
BACKGROUND: We conducted a retrospective cohort study to evaluate and compare the longitudinal effect of monotherapy with L-, L/T-, L/N-, and L/N/T-type calcium channel blockers (CCBs) on estimated glomerular filtration rate (eGFR), and to investigate the association of treatment duration with eGFR in diabetic patients with hypertension. METHODS: Using a clinical database, we identified new users of five CCBs, i.e. amlodipine (L-type, n = 693), nifedipine (L-type, n = 189), azelnidipine (L/T-type, n = 91), benidipine (L/N/T-type, n = 183), and cilnidipine (L/N-type, n = 61)...
June 3, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28573241/mechanisms-underlying-action-of-xinmailong-injection-a-traditional-chinese-medicine-in-cardiac-function-improvement
#8
Zhengtao Li, Sujuan Li, Lin Hu, Fang Li, Alex Chun Cheung, Weizai Shao, Yuling Que, George Pek-Heng Leung, Cui Yang
BACKGROUND: As a bioactive composite extracted from American cockroach, Xinmailong injection (XML) is used for the treatment of congestive heart failure (CHF) in China. Clinical data has provided evidence that XML has positive inotropic properties. The objective of this study was to assess the mechanisms involved in the therapeutical effect of XML on CHF. MATERIALS AND METHODS: The effects of XML on the cardiac function in isolated rat heart were measured. A Ca(2+) imaging technology was used in rat cardiomyocytes (H9c2 cells) to reveal the role of XML on Ca(2+) channels...
2017: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
https://www.readbyqxmd.com/read/28569435/the-new-kids-on-the-block-of-arrhythmogenic-disorders-short-qt-syndrome-and-early-repolarization
#9
REVIEW
Andrea Mazzanti, Katherine Underwood, Dmitriy Nevelev, Shanna Kofman, Silvia G Priori
Short QT Syndrome (SQTS) is a one of the rarest inheritable cardiac channelopathy, characterized by an accelerated cardiac repolarization, which is also the substrate for the development of life-threatening ventricular arrhythmias. Up to this date, fewer than 200 SQTS cases have been reported in the literature worldwide. Patients with SQTS may experience a cardiac arrest as early as in the neonatal period or as late as 80 years old. The cumulative probability of experiencing a cardiac arrest by the fifth decade of life approaches 40%, highlighting the importance of early recognition and management...
June 1, 2017: Journal of Cardiovascular Electrophysiology
https://www.readbyqxmd.com/read/28560432/otoprotective-effects-of-ethosuximide-in-nod-ltj-mice-with-age-related-hearing-loss
#10
Lu Sang, Tihua Zheng, Lingqian Min, Xiaolin Zhang, Xiufang Ma, Shami Entenman, Yipeng Su, Qingyin Zheng
Despite long-term efforts to elucidate the mechanisms responsible for age-related hearing loss (AHL), there is currently no available treatment strategy able to provide a cure. Apoptotic cell death, including that of hair cells and spiral ganglion neurons (SGNs) in the cochlea has been proposed to be the classic theory behind the development of AHL. As calcium signaling plays key roles in signal transduction in apoptosis, in this study, we selected ethosuximide, which is able to block T-type calcium (Ca2+ion) channels, suppressing Ca2+...
May 26, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28556246/cacna1g-is-a-genetic-modifier-of-epilepsy-in-a-mouse-model-of-dravet-syndrome
#11
Jeffrey D Calhoun, Nicole A Hawkins, Nicole J Zachwieja, Jennifer A Kearney
Dravet syndrome, an early onset epileptic encephalopathy, is most often caused by de novo mutation of the neuronal voltage-gated sodium channel gene SCN1A. Mouse models with deletion of Scn1a recapitulate Dravet syndrome phenotypes, including spontaneous generalized tonic-clonic seizures, susceptibility to seizures induced by elevated body temperature, and elevated risk of sudden unexpected death in epilepsy. Importantly, the epilepsy phenotype of Dravet mouse models is highly strain-dependent, suggesting a strong influence of genetic modifiers...
May 28, 2017: Epilepsia
https://www.readbyqxmd.com/read/28552652/blood-pressure-management-in-patients-with-diabetes-insights-from-the-diabetes-mellitus-status-in-canada-survey
#12
Jasmine Grenier, Shaun G Goodman, Lawrence A Leiter, Anatoly Langer, Hwee Teoh, Deepak L Bhatt, Alice Y Y Cheng, Mary K Tan, Thomas Ransom, Kim A Connelly, Andrew T Yan
OBJECTIVES: Optimal treatment of blood pressure (BP) and other cardiovascular risk factors, including hyperglycemia, is integral to diabetes management. There are limited data from the primary care setting concerning the contemporary and comprehensive management of type 2 diabetes and other cardiovascular risk factors in relation to guideline-recommended BP target achievement. METHODS: The Diabetes Mellitus Status in Canada (DM-SCAN) survey included 5172 ambulatory patients with type 2 diabetes...
May 25, 2017: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/28515322/g%C3%AE-%C3%AE-directly-modulates-vesicle-fusion-by-competing-with-synaptotagmin-for-binding-to-neuronal-snare-proteins-embedded-in-membranes
#13
Zack Zurawski, Brian Page, Michael C Chicka, Rebecca L Brindley, Christopher A Wells, Anita M Preininger, Karren Hyde, James A Gilbert, Osvaldo Cruz-Rodriguez, Kevin P M Currie, Edwin R Chapman, Simon Alford, Heidi E Hamm
Gi/o-coupled GPCRs can inhibit neurotransmitter release at synapses via multiple mechanisms. In addition to Gβγ-mediated modulation of voltage-gated calcium channels(VGCC), inhibition can also be mediated through the direct interaction of Gβγ subunits with the soluble N-ethylmaleimide attachment protein receptor (SNARE) complex of the vesicle fusion apparatus. Binding studies with soluble SNARE complexes have shown that Gβγ binds to both ternary SNARE complexes, t-SNARE heterodimers, and monomeric SNAREs, competing with synaptotagmin(syt)1 for binding sites on t-SNARE...
May 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28514017/isopimaric-acid-a-multi-targeting-ion-channel-modulator-reducing-excitability-and-arrhythmicity-in-a-spontaneously-beating-mouse-atrial-cell-line
#14
Sajjad Salari, Malin Silverå Ejneby, Johan Brask, Fredrik Elinder
AIM: Atrial fibrillation is the most common persistent cardiac arrhythmia, and it is not well controlled by present drugs. Because some resin acids open voltage-gated potassium channels and reduce neuronal excitability, we explored the effects of the resin acid isopimaric acid (IPA) on action potentials and ion currents in cardiomyocytes. METHODS: Spontaneously beating mouse atrial HL-1 cells were investigated with the whole-cell patch-clamp technique. RESULTS: 1-25 μmol L(-1) IPA reduced the action potential frequency by up to 50%...
May 17, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28512247/targetable-t-type-calcium-channels-drive-glioblastoma
#15
Ying Zhang, Nichola Cruickshanks, Fang Yuan, Baomin Wang, Mary Pahuski, Julia Wulfkuhle, Isela Gallagher, Alexander F Koeppel, Sarah Hatef, Christopher Papanicolas, Jeongwu Lee, Eli E Bar, David Schiff, Stephen Turner, Emanuel F Petricoin, Lloyd S Gray, Roger Abounader
Glioblastoma stem-like cells (GSC) promote tumor initiation, progression and therapeutic resistance. Here we show how GSC can be targeted by the FDA approved drug mibefradil which inhibits the T-type calcium channel Cav3.2. This calcium channel was highly expressed in human GBM specimens and enriched in GSC. Analyses of the TCGA and REMBRANDT databases confirmed upregulation of Cav3.2 in a subset of tumors and showed that overexpression associated with worse prognosis. Mibefradil treatment or RNAi-mediated attenuation of Cav3...
May 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28511346/potential-therapeutic-action-of-nitrite-in-sickle-cell-disease
#16
Nadeem Wajih, Swati Basu, Anuj Jailwala, Hee Won Kim, David Ostrowski, Andreas Perlegas, Crystal A Bolden, Nancy L Buechler, Mark T Gladwin, David L Caudell, Elaheh Rahbar, Martha A Alexander-Miller, Vidula Vachharajani, Daniel B Kim-Shapiro
Sickle cell disease is caused by a mutant form of hemoglobin that polymerizes under hypoxic conditions, increasing rigidity, fragility, calcium influx-mediated dehydration, and adhesivity of red blood cells. Increased red cell fragility results in hemolysis, which reduces nitric oxide (NO) bioavailability, and induces platelet activation and inflammation leading to adhesion of circulating blood cells. Nitric Oxide inhibits adhesion and platelet activation. Nitrite has emerged as an attractive therapeutic agent that targets delivery of NO activity to areas of hypoxia through bioactivation by deoxygenated red blood cell hemoglobin...
August 2017: Redox Biology
https://www.readbyqxmd.com/read/28506097/a-computational-model-of-the-ca-2-transients-and-influence-of-buffering-in-guinea-pig-urinary-bladder-smooth-muscle-cells
#17
Vijay Dave, Rohit Manchanda
Many cellular events including electrical activity and muscle contraction are regulated and coordinated by intracellular [Formula: see text] concentration ([[Formula: see text]][Formula: see text]. In detrusor smooth muscle (DSM) cells, [[Formula: see text]]i is normally maintained at very low levels and rises transiently during signalling processes as a result of (i) influx from the extracellular space (mainly via L-type and T-type [Formula: see text] channels) and (ii) [Formula: see text] release from sarcoplasmic reticulum (SR) into the cytoplasm...
April 20, 2017: Journal of Bioinformatics and Computational Biology
https://www.readbyqxmd.com/read/28504379/t-type-calcium-channels-as-potential-biomarkers-in-melanoma
#18
R A Ellis
No abstract text is available yet for this article.
May 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28494863/multiplexed-spike-coding-and-adaptation-in-the-thalamus
#19
Rebecca A Mease, Thomas Kuner, Adrienne L Fairhall, Alexander Groh
High-frequency "burst" clusters of spikes are a generic output pattern of many neurons. While bursting is a ubiquitous computational feature of different nervous systems across animal species, the encoding of synaptic inputs by bursts is not well understood. We find that bursting neurons in the rodent thalamus employ "multiplexing" to differentially encode low- and high-frequency stimulus features associated with either T-type calcium "low-threshold" or fast sodium spiking events, respectively, and these events adapt differently...
May 9, 2017: Cell Reports
https://www.readbyqxmd.com/read/28475719/neuritin-enhances-synaptic-transmission-in-medial-prefrontal-cortex-in-mice-by-increasing-cav3-3-surface-expression
#20
Jun-Mei Lu, Dong-Dong Liu, Zhao-Yang Li, Chen Ling, Yan-Ai Mei
Neuritin is a neurotrophic factor involved in neural development and synaptic plasticity. However, its role in modulating synaptic transmission remains unclear. Here, we investigated the effects of neuritin on miniature excitatory postsynaptic currents (mEPSCs) and glutamate release in the medial prefrontal cortex (mPFC) in mice. Incubation of mPFC slices with neuritin for 45 min significantly increased mEPSC frequency and glutamate release as measured by high-performance liquid chromatography, which was mimicked by insulin and abrogated by an insulin receptor (IR) inhibitor...
May 4, 2017: Cerebral Cortex
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