Abstract：
:It is well established that intracellular calcium ([Ca2+]i) controls the inotropic state of the myocardium, and evidence mounts that a "Ca2+ clock" controls the chronotropic state of the heart. Recent findings describe a calcium-activated nonselective cation channel (NSCCa) in various cardiac preparations sharing hallmark characteristics of the transient receptor potential melastatin 4 (TRPM4). TRPM4 is functionally expressed throughout the heart and has been implicated as a NSCCa that mediates membrane depolarization. However, the functional significance of TRPM4 in regards to Ca2+ signaling and its effects on cellular excitability and pacemaker function remains inconclusive. Here, we show by Fura2 Ca-imaging that pharmacological inhibition of TRPM4 in HL-1 mouse cardiac myocytes by 9-phenanthrol (10 μM) and flufenamic acid (10 and 100 μM) decreases Ca2+ oscillations followed by an overall increase in [Ca2+]i. The latter occurs also in HL-1 cells in Ca(2+)-free solution and after depletion of sarcoplasmic reticulum Ca2+ with thapsigargin (10 μM). These pharmacologic agents also depolarize HL-1 cell mitochondrial membrane potential. Furthermore, by on-cell voltage clamp we show that 9-phenanthrol reversibly inhibits membrane current; by fluorescence immunohistochemistry we demonstrate that HL-1 cells display punctate surface labeling with TRPM4 antibody; and by immunoblotting using this antibody we show these cells express a 130-150 kDa protein, as expected for TRPM4. We conclude that 9-phenanthrol inhibits TRPM4 ion channels in HL-1 cells, which in turn decreases Ca2+ oscillations followed by a compensatory increase in [Ca2+]i from an intracellular store other than the sarcoplasmic reticulum. We speculate that the most likely source is the mitochondrion.
journal_name
Cell Calciumjournal_title
Cell calciumauthors
Burt R,Graves BM,Gao M,Li C,Williams DL,Fregoso SP,Hoover DB,Li Y,Wright GL,Wondergem Rdoi
10.1016/j.ceca.2013.06.003subject
Has Abstractpub_date
2013-09-01 00:00:00pages
193-201issue
3eissn
0143-4160issn
1532-1991pii
S0143-4160(13)00088-2journal_volume
54pub_type
杂志文章相关文献
CELL CALCIUM文献大全abstract：:The mitochondrial permeability transition pore (mPTP) has long been known to have a role in mitochondrial calcium (Ca(2+)) homeostasis under pathological conditions as a mediator of the mitochondrial permeability transition and the activation of the consequent cell death mechanism. However, its role in the context of ...
journal_title：Cell calcium
pub_type： 杂志文章
doi：10.1016/j.ceca.2014.03.004
更新日期：2014-07-01 00:00:00
abstract：:Recent developments in microscopy and fluorescent indicators now make it possible to monitor the activity and localization of membrane ion channels by imaging Ca(2+) flux through individual channels. Such optical approaches have advantages over electrophysiological single-channel techniques in that they are less invas...
journal_title：Cell calcium
pub_type： 杂志文章
doi：10.1016/j.ceca.2004.10.008
更新日期：2005-04-01 00:00:00
abstract：:There is growing evidence indicating that the pore structure of voltage-gated ion channels (VGICs) influences gating besides their conductance. Regarding low voltage-activated (LVA) Ca2+ channels, it has been demonstrated that substitutions of the pore aspartate (D) by a glutamate (D-to-E substitution) in domains III ...
journal_title：Cell calcium
pub_type： 杂志文章
doi：10.1016/j.ceca.2020.102214
更新日期：2020-07-01 00:00:00
abstract：:We describe the construction of a high-resolution confocal laser-scanning microscope, and illustrate its use for studying elementary Ca2+ signalling events in cells. An avalanche photodiode module and simple optical path provide a high efficiency system for detection of fluorescence signals, allowing use of a small co...
journal_title：Cell calcium
pub_type： 杂志文章
doi：10.1016/s0143-4160(97)90055-5
更新日期：1997-06-01 00:00:00
abstract：:The Ca(2+) and cAMP/PKA pathways are the primary signaling systems in secretory epithelia that control virtually all secretory gland functions. Interaction and crosstalk in Ca(2+) and cAMP signaling occur at multiple levels to control and tune the activity of each other. Physiologically, Ca(2+) and cAMP signaling oper...
journal_title：Cell calcium
pub_type： 杂志文章,评审
doi：10.1016/j.ceca.2014.01.006
更新日期：2014-06-01 00:00:00
abstract：:The Bcl-2 protein, best known for its ability to inhibit apoptosis, interacts with the inositol 1,4,5-trisphosphate receptor (IP(3)R) Ca(2+) channel to regulate IP(3)-mediated Ca(2+) release from the endoplasmic reticulum. This review summarizes the current state of knowledge regarding the interaction of Bcl-2, and al...
journal_title：Cell calcium
pub_type： 杂志文章,评审
doi：10.1016/j.ceca.2011.05.011
更新日期：2011-09-01 00:00:00
abstract：:The concentration of free Ca2+ in the cytoplasm and organelles of individual mouse pancreatic beta-cells was estimated with dual wavelength microfluorometry and the indicators Fura-2 and furaptra. Measuring the increase of cytoplasmic Ca2+ resulting from intracellular mobilization of the ion in ob/ob mouse beta-cells,...
journal_title：Cell calcium
pub_type： 杂志文章
doi：10.1054/ceca.1999.0087
更新日期：2000-01-01 00:00:00
abstract：:Sarcoplasmic reticulum contains the internal Ca(2+) store in smooth muscle cells and its lumen appears to be a continuum that lacks diffusion barriers. Accordingly, the free luminal Ca(2+) level is the same all throughout the SR; however, whether the Ca(2+) buffer capacity is the same in all the SR is unknown. We have...
journal_title：Cell calcium
pub_type： 杂志文章
doi：10.1016/j.ceca.2009.07.005
更新日期：2009-09-01 00:00:00
abstract：:To determine intracellular Ca2+ concentrations more accurately, we examined Kd of Fura-2 for Ca2+ in conditions which were systemically changed. In a solution comprising of 150 mM KCI, 20 mM MOPS-KOH, pH 6.94, 60-100 microM EGTA and 1 microM Fura-2, Kd at 20 degrees C was 0.266 +/- 0.016 microM (mean +/- SEM) (21 dete...
journal_title：Cell calcium
pub_type： 杂志文章
doi：10.1016/0143-4160(91)90082-p
更新日期：1991-01-01 00:00:00
abstract：:TRPA1, a Ca(2+)-permeable cation channel that is expressed in sensory neurones, is involved in the perception of chemical irritants and mechanical hyperalgesia. TRPA1 is activated by either covalent or reversible binding of various chemical compounds, including allylisothiocyanate or acrolein, and is further sensitise...
journal_title：Cell calcium
pub_type： 杂志文章
doi：10.1016/j.ceca.2008.08.001
更新日期：2009-02-01 00:00:00
abstract：:Isolated avian growth plate chondrocytes convert the acetoxymethyl ester (AM) form of Fura-2 quickly and efficiently to the Ca2(+)-sensitive pentacarboxylic acid (FA) form. Control experiments indicate that the Kd for intracellular Fura-2/FA is very close to that of extracellular Fura-2/FA at the same ionic strength a...
journal_title：Cell calcium
pub_type： 杂志文章
doi：10.1016/0143-4160(90)90077-8
更新日期：1990-08-01 00:00:00
abstract：:N,N'-dicyclohexylcarbodiimide (DCCD) and 1-cyclohexyl-3-(2-morpholinoethyl) carbodiimide (CMCD) inhibited calmodulin-dependent Ca2(+)+Mg2(+)-ATPase activity in erythrocyte ghost membranes. The extent of the inhibition caused by carbodiimides strongly depended on their hydrophobicity. Hydrophobic DCCD was a more potent...
journal_title：Cell calcium
pub_type： 杂志文章
doi：10.1016/0143-4160(90)90004-e
更新日期：1990-04-01 00:00:00
abstract：:Corticosteroid hormones, which are released in high amounts after stress, easily pass the blood-brain-barrier. In the brain they bind to intracellular receptors which act as transcriptional regulators. These receptors are highly expressed in neurons of the hippocampal formation and the amygdala, areas that play a role...
journal_title：Cell calcium
pub_type： 杂志文章,评审
doi：10.1016/j.ceca.2011.11.002
更新日期：2012-03-01 00:00:00
abstract：:Calcium and calcium-dependent systems have been long implicated in the induction of epilepsy. We have previously observed that intracellular calcium ([Ca2+]i) levels remain elevated in cells undergoing epileptogenesis in the hippocampal neuronal culture (HNC) model. In this study, we employed the hippocampal neuronal ...
journal_title：Cell calcium
pub_type： 杂志文章
doi：10.1054/ceca.2000.0146
更新日期：2000-09-01 00:00:00
abstract：:The lack of specific inhibitors of the plasma membrane Ca2+ pump (PMCA) has made vanadate (VO3-), a non-specific inhibitor, an invaluable tool in the study of PMCA function. However, three important properties of vanadate as an inhibitor of the PMCA in intact cells, namely its speed of action in different experimental...
journal_title：Cell calcium
pub_type： 杂志文章
doi：10.1054/ceca.2001.0241
更新日期：2001-11-01 00:00:00
abstract：:We describe experiments in which the low affinity indicator Oregon Green BAPTA 5N was used to record the spatially resolved changes in [Ca(2+)] from intracellular stores in rat gastric myocytes. Cells were loaded with the membrane permeant form of the indicator and imaged using a confocal scanning laser microscope. In...
journal_title：Cell calcium
pub_type： 杂志文章
doi：10.1054/ceca.2001.0269
更新日期：2002-04-01 00:00:00
abstract：:Several potentially life-threatening cardiovascular and respiratory disorders result in prolonged deprivation of oxygen, which in turn results in significant cellular adaptation, or remodelling. An important component of this functional adaptation arises as a direct consequence of altered ion channel expression by chr...
journal_title：Cell calcium
pub_type： 杂志文章,评审
doi：10.1016/j.ceca.2004.02.005
更新日期：2004-09-01 00:00:00
abstract：:The mechanism by which the depletion of intracellular Ca2+ stores stimulates Ca2+ influx is poorly understood. However, the coupling of depletion to influx is broken during mitosis [Preston, S.F. et. al., (1991) Cell Regul., 2, 915-925]. Thus, in interphase HeLa cells, activation of the histamine H1 receptor, or incub...
journal_title：Cell calcium
pub_type： 杂志文章
doi：10.1016/0143-4160(93)90042-5
更新日期：1993-05-01 00:00:00
abstract：:Calcium dependence of bleb formation and cell death was evaluated in rat hepatocytes following ATP depletion by metabolic inhibition with KCN and iodoacetate ('chemical hypoxia'). Cytosolic free Ca2+ was measured in single cells by ratio imaging of Fura-2 fluorescence using multiparameter digitized video microscopy. C...
journal_title：Cell calcium
pub_type： 杂志文章
doi：10.1016/0143-4160(88)90004-8
更新日期：1988-12-01 00:00:00
abstract：:Cooling can induce Ca(2+) signaling via activation of temperature-sensitive ion channels such as TRPM8, TRPA1 and ryanodine receptor channels. Here we have studied the mechanism of cooling-evoked Ca(2+) signaling in mouse olfactory ensheathing cells (OECs), a specialized type of glial cells in the olfactory nerve laye...
journal_title：Cell calcium
pub_type： 杂志文章
doi：10.1016/j.ceca.2012.04.017
更新日期：2012-08-01 00:00:00
abstract：:Hepatocytes stimulated with calcium-mobilising agonists generate free Ca transients whose frequency is modulated by hormone concentration. Importantly, the time-course of individual free Ca transients is independent of agonist dose but does change with agonist species. A receptor-controlled model in which protein kina...
journal_title：Cell calcium
pub_type： 杂志文章,评审
doi：10.1016/0143-4160(91)90011-3
更新日期：1991-02-01 00:00:00
abstract：:It has been reported that leukotriene B4 can translocate calcium across model membranes (Serhan et. al., (1982) J. Biol. Chem., 257: 4746). Such ionophoretic behavior could account for its biological effects. We have examined the effect of chromatographically pure leukotriene B4 on Ca2+ permeability when added exogeno...
journal_title：Cell calcium
pub_type： 杂志文章
doi：10.1016/0143-4160(87)90028-5
更新日期：1987-12-01 00:00:00
abstract：:Rabbit gall-bladder epithelial cells were isolated by a combination of Ca2+ omission, enzymatic treatment, and mechanical detachment and had a viability of 96-98% and well preserved morphology. Measurements of cytosolic free Ca2+ concentration ([Ca2+]i) in these cells with the Ca2+-fluorescent indicator fura-2 demonst...
journal_title：Cell calcium
pub_type： 杂志文章
doi：10.1016/0143-4160(89)90042-0
更新日期：1989-01-01 00:00:00
abstract：:Cellular senescence is a stable cell proliferation arrest induced by a variety of stresses including telomere shortening, oncogene activation and oxidative stress. This process plays a crucial role in many physiopathological contexts, especially during aging when cellular senescence favors development of age-related d...
journal_title：Cell calcium
pub_type： 杂志文章,评审
doi：10.1016/j.ceca.2017.04.001
更新日期：2018-03-01 00:00:00
abstract：:Relative to mammals, the neuroendocrine control of pituitary growth hormone (GH) secretion and synthesis in teleost fish involves numerous stimulatory and inhibitory regulators, many of which are delivered to the somatotrophs via direct innervation. Among teleosts, how multifactorial regulation of somatotroph function...
journal_title：Cell calcium
pub_type： 杂志文章,评审
doi：10.1016/j.ceca.2011.11.001
更新日期：2012-03-01 00:00:00
abstract：:Infrared neural stimulation (INS) is a promising neurostimulation technique that can activate neural tissue with high spatial precision and without the need for exogenous agents. However, little is understood about how infrared light interacts with neural tissue on a cellular level, particularly within the living brai...
journal_title：Cell calcium
pub_type： 杂志文章
doi：10.1016/j.ceca.2014.01.004
更新日期：2014-04-01 00:00:00
abstract：:STIM and Orai isoforms orchestrate store operated Ca2+ entry (SOCE) and thus cytosolic Ca2+ fluctuations following stimulation by hormones, growth factors and further mediators. Orai1 is a target of Nedd4-2, an ubiquitin ligase preparing several plasma membrane proteins for degradation. Phosphorylation of Nedd4-2 by t...
journal_title：Cell calcium
pub_type： 杂志文章,评审
doi：10.1016/j.ceca.2012.05.005
更新日期：2012-11-01 00:00:00
abstract：:In addition to its role in artery contraction, Rho kinase (ROCK) is reported to be involved in the Ca(2+) response to vasoconstrictor agonist in rat aorta. However the signaling pathway mediated by ROCK had not been investigated so far and it was not known whether ROCK also contributed to Ca(2+) signaling in cultured ...
journal_title：Cell calcium
pub_type： 杂志文章
doi：10.1016/j.ceca.2012.07.002
更新日期：2012-12-01 00:00:00
abstract：:NAADP is a potent regulator of cytosolic calcium levels. Much evidence suggests that NAADP activates a novel channel located on an acidic (lysosomal-like) calcium store, the mobilisation of which results in further calcium release from the endoplasmic reticulum. Here, we discuss the recent identification of a family o...
journal_title：Cell calcium
pub_type： 杂志文章,评审
doi：10.1016/j.ceca.2010.05.001
更新日期：2010-06-01 00:00:00
abstract：:When Xenopus oocytes injected with rat brain poly(A)+RNA were voltage-clamped in a recording solution containing Ca2+, a depolarization pulse induced a transient current, ICl(Ca), which reflects calmodulin-mediated opening of endogenous Cl- channels in response to a Ca2+ influx through Ca2+ channels of brain origin. I...
journal_title：Cell calcium
pub_type： 杂志文章
doi：10.1016/0143-4160(90)90008-i
更新日期：1990-04-01 00:00:00
