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Voltage-dependent calcium channels

Donal Melanaphy, Christpher D Johnson, Maxim Kustov, Connall Watson, Lyudmyla Borysova, Theodore Burdyga, Alexander V Zholos
Transient receptor potential melastatin 8 (TRPM8) is the principal cold and menthol receptor channel. Characterized primarily for its cold sensing role in sensory neurons, it is expressed and functional in several non-neuronal tissues, including vasculature. We previously demonstrated that menthol causes vasoconstriction and vasodilatation in isolated arteries, depending on vascular tone. Here we investigated calcium's role in responses mediated by TRPM8 ligands in rat tail artery myocytes using patch-clamp electrophysiology and ratiometric Ca(2+) recording...
October 7, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Rajeev B Tajhya, Xueyou Hu, Mark R Tanner, Redwan Huq, Natee Kongchan, Joel R Neilson, George G Rodney, Frank T Horrigan, Lubov T Timchenko, Christine Beeton
Myoblasts are mononucleated precursors of myofibers; they persist in mature skeletal muscles for growth and regeneration post injury. During myotonic dystrophy type 1 (DM1), a complex autosomal-dominant neuromuscular disease, the differentiation of skeletal myoblasts into functional myotubes is impaired, resulting in muscle wasting and weakness. The mechanisms leading to this altered differentiation are not fully understood. Here, we demonstrate that the calcium- and voltage-dependent potassium channel, KCa1...
October 20, 2016: Cell Death & Disease
A Andrade, J Hope, A Allen, V Yorgan, D Lipscombe, J Q Pan
CACNA1I is a candidate schizophrenia risk gene. It encodes the pore-forming human CaV3.3 α1 subunit, a subtype of voltage-gated calcium channel that contributes to T-type currents. Recently, two de novo missense variations, T797M and R1346H, of hCaV3.3 were identified in individuals with schizophrenia. Here we show that R1346H, but not T797M, is associated with lower hCaV3.3 protein levels, reduced glycosylation, and lower membrane surface levels of hCaV3.3 when expressed in human cell lines compared to wild-type...
October 19, 2016: Scientific Reports
Young Youp Koh, Dong Yoon Lim
OBJECTIVE: The present study was aimed to investigate the characteristics of simvastatin, one of statins, on the catecholamine (CA) secretion from the perfused model of the isolated rat adrenal gland, and also to clarify its mechanism of action. DESIGN AND METHOD: The adrenal gland was isolated and perfused with Krebs-bicarbonate. CA was measured directly by using the fluorospectrophotometer. RESULTS: Simvastatin inhibited ACh-evoked CA secretory response in a dose- and time-dependent fashion...
September 2016: Journal of Hypertension
Michal Behuliak, Michal Bencze, Anna Vavrinova, Ivana Vaneckova, Josef Zicha
OBJECTIVE: Voltage-dependent calcium channels (VDCCs) play an important role in two major abnormalities observed in spontaneously hypertensive rats (SHR) - hyperactivity of sympathetic nervous system (SNS) and enhanced Ca influx to vascular smooth muscle cells (VSMC). α2δ subunit of VDCC, which promotes surface trafficking and modulates the biophysical properties of VDCC, was identified as a critical component of increased L-type VDCC calcium currents in arterial myocytes of SHR. On the other hand, N-type VDCCs control a neurotransmitter release in the peripheral sympathetic nervous system and play an important role in sympathetic hyperactivity in SHR...
September 2016: Journal of Hypertension
Josef Zicha, Michal Behuliak, Ivana Vaneckova
OBJECTIVE: Comparing BP response to Ca channel opener BAY K8644 prior and after Rho kinase inhibition we demonstrated lowered calcium sensitization in spontaneously hypertensive rats (SHR), although BP response of intact SHR to Rho kinase inhibitor fasudil was enhanced (Behuliak et al. J Hypertens 31:2025,2013). The aim of the present study was to evaluate calcium sensitization in hypertensive TGR and their normotensive HanSD controls using the same methods. We also tried to elucidate the interference of baroreflex-activated sympathetic activity with BP response to fasudil...
September 2016: Journal of Hypertension
Nan Zhang, Shengchang Yang, Chang Wang, Jianghua Zhang, Lifang Huo, Yiru Cheng, Chuan Wang, Zhanfeng Jia, Leiming Ren, Lin Kang, Wei Zhang
Alzheimer's disease (AD) and type II diabetes mellitus (DM2) are the most common aging-related diseases and are characterized by β-amyloid and amylin accumulation, respectively. Multiple studies have indicated a strong correlation between these two diseases. Amylin oligomerization in the brain appears to be a novel risk factor for developing AD. Although amylin aggregation has been demonstrated to induce cytotoxicity in neurons through altering Ca(2+) homeostasis, the underlying mechanisms have not been fully explored...
October 12, 2016: Neuropharmacology
Zoltan Patai, Andras Guttman, Endre G Mikus
Drotaverine is considered to evoke a spasmolytic effect through the inhibition of cyclic-3',5'-nucleotide-phophodiesterase (PDE) enzymes. However, published receptor binding data supports the potential L-type Voltage Operated Calcium Channel (L-VOCC) blocking effect of drotaverine as well. Hence, in this work we are focusing on the potential L-VOCC blocking effect of drotaverine using L-VOCC associated functional in vitro models. Accordingly, drotaverine and reference agents were tested on KCl-induced guinea pig tracheal contraction...
October 13, 2016: Journal of Pharmacology and Experimental Therapeutics
Izaskun Buendia, Giammarco Tenti, Patrycja Michalska, Iago Méndez-López, Enrique Luengo, Michele Satriani, Juan Fernando Padin Nogueira, Manuela G López, María Teresa Ramos, Antonio G García, J Carlos Menéndez, Rafael León
During brain ischemia, oxygen and glucose deprivation induces calcium overload, extensive oxidative stress, neuroinflammation and, finally, massive neuronal loss. In the search of a neuroprotective compound to mitigate this neuronal loss, we have designed and synthesized a new multitarget hybrid (ITH14001) directed at the reduction of calcium overload by acting on two regulators of calcium homeostasis; the mitochondrial Na+/Ca2+ exchanger (mNCX) and L-type voltage dependent calcium channels (VDCCs). This compound is a hybrid of CGP37157 (mNCX inhibitor) and nimodipine (L-type VDCCs blocker), and its pharmacological evaluation revealed a moderate ability to selectively inhibit both targets...
October 12, 2016: ACS Chemical Neuroscience
Harry Z E Greenberg, Kazi S Jahan, Jian Shi, W-S Vanessa Ho, Anthony P Albert
The present study investigates the effect of commonly used negative and positive allosteric modulators of the calcium-sensing receptor (CaSR) on vascular reactivity. In wire myography studies, increasing [Ca(2+)]o from 1mM to 6mM induced concentration-dependent relaxations of methoxamine-induced pre-contracted rabbit mesenteric arteries, with 6mM [Ca(2+)]o producing almost complete relaxation. [Ca(2+)]o-induced relaxations were attenuated in the presence of the calcilytics Calhex-231 and NPS 2143, and abolished by the removal of the endothelium...
October 8, 2016: European Journal of Pharmacology
Deepika Sharma, Brijendra Kumar Tiwari, Subhash Mehto, Cecil Antony, Gunjan Kak, Yogendra Singh, Krishnamurthy Natarajan
The prevalence of Mycobacterium tuberculosis (M. tb) strains eliciting drug resistance has necessitated the need for understanding the complexities of host pathogen interactions. The regulation of calcium homeostasis by Voltage Gated Calcium Channel (VGCCs) upon M. tb infection has recently assumed importance in this area. We previously showed a suppressor role of VGCC during M. tb infections and recently reported the mechanisms of its regulation by M. tb. Here in this report, we further characterize the role of VGCC in mediating defence responses of macrophages during mycobacterial infection...
2016: PloS One
Sabine Nafzger, Jean-Sebastien Rougier
AIM: The L-type voltage-gated calcium channel Cav1.2 mediates the calcium influx into cells upon membrane depolarization. The list of cardiopathies associated to Cav1.2 dysfunctions highlights the importance of this channel in cardiac physiology. Calcium/calmodulin-dependent serine protein kinase (CASK), expressed in cardiac cells, has been identified as a regulator of Cav2.2 channels in neurons, but no experiments have been performed to investigate its role in Cav1.2 regulation. METHODS AND RESULTS: Full length or the distal C-terminal truncated of the pore-forming Cav1...
October 5, 2016: Cell Calcium
Andrei Rozov, Nail Burnashev
Suppression of NMDA receptor (NMDAR)-mediated currents by intracellular Ca(2+) has been described as a negative feedback loop in NMDAR modulation. In the time scale of tenths of milliseconds the depth of the suppression does not depend on the Ca(2+) source. It may be caused by Ca(2+) influx through voltage-gated calcium channels, NMDAR channels or release from intracellular stores. However, NMDARs are often co-expressed in synapses with Ca(2+)-permeable AMPA receptors (AMPARs). Due to significant differences in activation kinetics between these two types of glutamate receptors (GluRs), Ca(2+) entry through AMPARs precedes full activation of NMDARs, and therefore, might have an impact on the amplitude of NMDAR-mediated currents...
September 28, 2016: Cell Calcium
János Brunner, János Szabadics
We report that back-propagating action potentials (bAPs) are not simply digital feedback signals in dendrites but also carry analogue information about the overall state of neurons. Analogue information about the somatic membrane potential within a physiological range (from -78 to -64 mV) is retained by bAPs of dentate gyrus granule cells as different repolarization speeds in proximal dendrites and as different peak amplitudes in distal regions. These location-dependent waveform changes are reflected by local calcium influx, leading to proximal enhancement and distal attenuation during somatic hyperpolarization...
October 5, 2016: Nature Communications
Ksenia Blinova, Jayna Stohlman, Jose Vicente, Dulciana Chan, Lars Johannesen, Maria P Hortigon-Vinagre, Victor Zamora, Godfrey Smith, William J Crumb, Li Pang, Beverly Lyn-Cook, James Ross, Mathew Brock, Stacie Chvatal, Daniel Millard, Loriano Galeotti, Norman Stockbridge, David G Strauss
BACKGROUND: Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) hold promise for assessment of drug-induced arrhythmias and are being considered for use under the Comprehensive in Vitro Proarrhythmia Assay (CiPA). METHODS AND RESULTS: We studied the effects of 26 drugs and 3 drug combinations on two commercially available iPSC-CM types using high-throughput voltage-sensitive dye (VSD) and microelectrode-array (MEA) assays being studied for the Comprehensive in Vitro Proarrhythmia Assessment (CiPA) initiative and compared the results to clinical QT prolongation and torsade de pointes (TdP) risk...
October 3, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
Yulong Chen, Hongmei Zhang, Huanhuan Liu, Ailan Cao
Independent of its lipid-lowering properties, simvastatin (Sim) induces vasorelaxation; however, the underlying mechanisms have remained elusive. The aim of the present study was to investigate the vasorelaxant effects of Sim on rat superior mesenteric arteries and the mechanisms involved. The isometric tension of rat superior mesenteric arterial rings was recorded in vitro on a myograph. The results showed that Sim concentration-dependently relaxed the superior mesenteric artery rings with endothelium pre-contracted by phenylephrine hydrochloride [maximum relaxation (Emax)=51...
October 2016: Biomedical Reports
Yulong Chen, Cangbao Xu, Yahui Wei, Yaping Zhang, Ailan Cao
Resveratrol (Res) is a specific agonist of sirtuin 1, and has many cardioprotective effects. Although Res is able to relax various vascular beds, its pharmacological properties in rat superior mesenteric arteries and the underlying mechanism are not well clarified. The aim of present study was to investigate the vasorelaxant effects of Res on rat superior mesenteric arteries and the mechanisms involved. The isometric tension of rat superior mesenteric arterial rings was recorded in vitro using myography. It was found that Res concentration-dependently relaxed endothelium-intact superior mesenteric artery rings pre-contracted by phenylephrine hydrochloride (Emax, 97...
October 2016: Experimental and Therapeutic Medicine
Francisco J Urbano, Brennon R Luster, Stasia D'Onofrio, Susan Mahaffey, Edgar Garcia-Rill
Synaptic efferents from the PPN are known to modulate the neuronal activity of several intralaminar thalamic regions (e.g., the centrolateral/parafascicular; Cl/Pf nucleus). The activation of either the PPN or Cl/Pf nuclei in vivo has been described to induce the arousal of the animal and an increment in gamma band activity in the cortical electroencephalogram (EEG). The cellular mechanisms for the generation of gamma band oscillations in Reticular Activating System (RAS) neurons are the same as those found to generate gamma band oscillations in other brains nuclei...
2016: Journal of Visualized Experiments: JoVE
Hye-Jin Boo, Hye-Young Min, Hyun-Ji Jang, Hye Jeong Yun, John Kendal Smith, Quanri Jin, Hyo-Jong Lee, Diane Liu, Hee-Seok Kweon, Carmen Behrens, J Jack Lee, Ignacio I Wistuba, Euni Lee, Waun Ki Hong, Ho-Young Lee
Nicotinic acetylcholine receptors (nAChRs) binding to the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces Ca(2+) signalling, a mechanism that is implicated in various human cancers. In this study, we investigated the role of NNK-mediated Ca(2+) signalling in lung cancer formation. We show significant overexpression of insulin-like growth factors (IGFs) in association with IGF-1R activation in human preneoplastic lung lesions in smokers. NNK induces voltage-dependent calcium channel (VDCC)-intervened calcium influx in airway epithelial cells, resulting in a rapid IGF2 secretion via the regulated pathway and thus IGF-1R activation...
2016: Nature Communications
Nahit Rizaner, Rustem Onkal, Scott P Fraser, Alessandro Pristerá, Kenji Okuse, Mustafa B A Djamgoz
The possible association of intracellular Ca(2+) with metastasis in human cancer cells is poorly understood. We have studied Ca(2+) signaling in human prostate and breast cancer cell lines of strongly versus weakly metastatic potential in a comparative approach. Intracellular free Ca(2+) was measured using a membrane-permeant fluorescent Ca(2+)-indicator dye (Fluo-4 AM) and confocal microscopy. Spontaneous Ca(2+) oscillations were observed in a proportion of strongly metastatic human prostate and breast cancer cells (PC-3M and MDA-MB-231, respectively)...
October 2016: European Biophysics Journal: EBJ
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