Sixty years elapsed since Chang (Hsiang-Tung Chang, Xiang-Tong Zhang) presented his seminal report "Cortical neurons with particular reference to the apical dendrite" at the Cold Spring Harbor Symposium. Thanks to the development of elaborated techniques through the 6 decades, our understanding of the dendrite has been pushed forward greatly: the backward and forward conductions during excitation, sodium and calcium conductances, chemical excitation by uncaging glutamate at a dimension of micrometer, and the quantitative study of chemical organization of postsynaptic density (PSD), etc. Though the progression is great, there are still tough problems in dendritic research, especially the integration through dendritic spine.
Calcium Signaling ; Dendrites ; physiology ; Glutamic Acid ; metabolism

No abstract available.
Animal ; Calcium Signaling/physiology* ; Exocytosis/physiology ; Pancreas/physiology* ; Pancreas/cytology

Store-operated calcium entry (SOCE), a major mode of extracellular calcium entry, plays roles in a variety of cell activities. Accumulating evidence indicates that the intracellular calcium ion concentration and calcium signaling are critical for the responses induced by oxidative stress. The present study was designed to investigate the potential effect of SOCE inhibition on H₂O₂-induced apoptosis in endothelial progenitor cells (EPCs), which are the predominant cells involved in endothelial repair. The results showed that H₂O₂-induced EPC apoptosis was reversed by SOCE inhibition induced either using the SOCE antagonist ML-9 or via silencing of stromal interaction molecule 1 (STIM1), a component of SOCE. Furthermore, SOCE inhibition repressed the increases in intracellular reactive oxygen species (ROS) levels and endoplasmic reticulum (ER) stress and ameliorated the mitochondrial dysfunction caused by H₂O₂. Our findings provide evidence that SOCE inhibition exerts a protective effect on EPCs in response to oxidative stress induced by H₂O₂ and may serve as a potential therapeutic strategy against vascular endothelial injury.
Apoptosis* ; Calcium Signaling ; Calcium* ; Endoplasmic Reticulum ; Endothelial Progenitor Cells* ; Oxidative Stress ; Reactive Oxygen Species

Lysophosphatidylethanolamine (LPE), a lyso-type metabolite of phosphatidylethanolamine, has been reported to be an intercellular signaling molecule. LPE mobilizes intracellular Ca²⁺ through G-protein-coupled receptor (GPCR) in some cells types. However, GPCRs for lysophosphatidic acid (LPA) were not implicated in the LPE-mediated activities in LPA GPCR overexpression systems or in SK-OV3 ovarian cancer cells. In the present study, in human SH-SY5Y neuroblastoma cells, experiments with LPA₁ antagonists showed LPE induced intracellular Ca²⁺ increases in an LPA₁ GPCR-dependent manner. Furthermore, LPE increased intracellular Ca²⁺ through pertussis-sensitive G proteins, edelfosine-sensitive-phospholipase C, 2-APB-sensitive IP₃ receptors, Ca²⁺ release from intracellular Ca²⁺ stores, and subsequent Ca²⁺ influx across plasma membranes, and LPA acted on LPA₁ and LPA₂ receptors to induce Ca²⁺ response in a 2-APB-sensitive and insensitive manner. These findings suggest novel involvements for LPE and LPA in calcium signaling in human SH-SY5Y neuroblastoma cells.
Calcium Signaling* ; Calcium* ; Cell Membrane ; GTP-Binding Proteins ; Humans* ; Neuroblastoma* ; Ovarian Neoplasms

It has been reported that activation of metabotropic glutamate receptor 1 (mGluR1) can mediate endocannabinoid-induced short-term depression of synaptic transmission in cerebellar parallel fiber (PF)-Purkinje cell (PC) synapse. mGluR1 has signaling pathways involved in intracellular calcium increase which may contribute to endocannabinoid release. Two major mGluR1-evoked calcium signaling pathways are known: (1) slow-kinetic inward current carried by transient receptor potential canonical (TRPC) channel which is permeable to Ca2+; (2) IP3-induced calcium release from intracellular calcium store. However, it is unclear how much each calcium source contributes to endocannabinoid signaling. Here, we investigated whether calcium influx through mGluR1-evoked TRPC channel contributes to endocannabinoid signaling in cerebellar Purkinje cells. At first, we applied SKF96365 to inhibit TRPC, which blocked endocannabinoid-induced short-term depression completely. However, an alternative TRP channel inhibitor, BTP2 did not affect endocannabinoid-induced short-term depression although it blocked mGluR1-evoked TRPC currents. Endocannabinoid signaling occurred normally even though the TRPC current was mostly blocked by BTP2. Our data imply that TRPC current does not play an important role in endocannabinoid signaling. We also suggest precaution in applying SKF96365 to inhibit TRP channels and propose BTP2 as an alternative TRPC inhibitor.
Calcium ; Calcium Signaling ; Cerebellum ; Depression ; Endocannabinoids ; Imidazoles ; Purkinje Cells ; Receptors, Metabotropic Glutamate ; Synapses ; Synaptic Transmission

Recent human genetic studies have shown that Gβ5 is related to various clinical symptoms, such as sinus bradycardia, cognitive disability, and attention deficit hyperactivity disorder. Although the calcium signaling cascade is closely associated with a heterotrimeric G-protein, the function of Gβ5 in calcium signaling and its relevance to clinical symptoms remain unknown. In this study, we investigated the in vitro changes of store-operated calcium entry (SOCE) with exogenous expression of Gβ5. The cells expressing Gβ5 had enhanced SOCE after depletion of calcium ion inside the endoplasmic reticulum. Gβ5 also augmented Stim1- and Orai1-dependent SOCE. An ORAI1 loss-of-function mutant did not show inhibition of Gβ5-induced SOCE, and a STIM1-ERM truncation mutant showed no enhancement of SOCE. These results suggested a novel role of GNB5 and Stim1, and provided insight into the regulatory mechanism of SOCE.
Attention Deficit Disorder with Hyperactivity ; Bradycardia ; Calcium ; Calcium Signaling ; Endoplasmic Reticulum ; GTP-Binding Proteins ; Humans ; In Vitro Techniques

A stochastic model of intracellular calcium oscillations is put forward by taking into account the random opening-closing of Ca2+ channels in endoplasmic reticulum (ER) membrane. The numerical results of the stochastic model show simple and complex calcium oscillations, which accord with the experiment results.
Calcium Channels/*metabolism ; *Calcium Signaling ; Endoplasmic Reticulum/*metabolism ; Intracellular Space ; Kinetics ; Mathematics ; Models, Biological ; Stochastic Processes

Transient receptor potential (TRP) ion channels are widely distributed in different kinds of cells. TRP expresses highly in the prostatic cancer epithelia at different levels, but whether it expresses in chronic prostatitis epithelia or not remains poorly understood. Investigating the roles of TRP ion channels in the pathogenesis of prostatic diseases could afford us a new approach to their diagnosis and therapy.
Calcium Channels ; Calcium Signaling ; Humans ; Male ; Prostatic Diseases ; metabolism ; pathology ; Transient Receptor Potential Channels

Voltage gated calcium channels (VGCCs) are multi-subunit membrane proteins present in a variety of tissues and control many essential physiological processes. Due to their vital importance, VGCCs are regulated by a myriad of proteins and signaling pathways. Here we review the literature on the regulation of VGCCs by proteolysis of the pore-forming α1 subunit, Ca(v)α(1). This form of regulation modulates channel function and degradation and affects cellular gene expression and excitability. L-type Ca(2+) channels are proteolyzed in two ways, depending on tissue localization. In the heart and skeletal muscle, the distal C-terminus of Ca(v)α(1) is cleaved and acts as an autoinhibitor when it reassociates with the proximal C-terminus. Relief of this autoinhibition underlies the β-adrenergic stimulation-induced enhancement of cardiac and skeletal muscle calcium currents, part of the "fight or flight" response. Proteolysis of the distal C-terminus of L-type channels also occurs in the brain and is probably catalyzed by a calpain-like protease. In some brain regions, the entire C-terminus of L-type Ca(2+) channels can be cleaved by an unknown protease and translocates to the nucleus acting as a transcription factor. The distal C-terminus of P/Q-channel Ca(v)α(1) is also proteolyzed and translocates to the nucleus. Truncated forms of the PQ-channel Ca(v)α(1) are produced by many disease-causing mutations and interfere with the function of full-length channels. Truncated forms of N-type channel Ca(v)α(1), generated by mutagenesis, affect the expression of full-length channels. New forms of proteolysis of VGCC subunits remain to be discovered and may represent a fruitful area of VGCC research.
Animals ; Calcium Channels, L-Type ; metabolism ; Calcium Signaling ; Humans ; Muscle, Skeletal ; physiology ; Proteolysis

OBJECTIVETo investigate the effects of power frequency magnetic field on the Ca2+ transport dynamics of isolated sarcoplasmic reticulum vesicles.

METHODSThe assays of Ca2+ uptake time course and the Ca2+-ATPase activity of sarcoplasmic reticulum vesicles were investigated by using dynamic mode of spectrometry with a Ca2+ dye; Ca2+ release channel activation was examined by 3H-ryanodine binding and Ca2+ release assays; membrane fluidity of sarcoplasmic reticulum vesicles was examined by fluorescence polarization, without or with exposure to the vesicles at a 0.4 mT, 50 Hz sinusoidal magnetic field.

RESULTS0.4 mT, 50 Hz sinusoidal magnetic field exposure caused about a 16% decline of the initial Ca2+ uptake rate from a (29.18 +/- 3.90) pmol.mg(-1).s(-1) to a (24.60 +/- 3.81) pmol.mg(-1).s(-1) and a 26% decline of the Ca2+-ATPase activity from (0.93 +/- 0.05) micromol.mg(-1).min(-1) to (0.69 +/- 0.07) micromol.mg(-1).min(-1) of sarcoplasmic reticulum vesicles, whereas caused a 15% increase of the initial Ca2+ release rate from (4.83 +/- 0.82) pmol.mg(-1).s(-1) to (5.65 +/- 0.43) pmol.mg(-1).s(-1) and a 5% increase in 3H-ryanodine binding to the receptor from (1.10 +/- 0.12) pmol/mg to (1.16 +/- 0.13) pmol/mg, respectively.

CONCLUSIONThe decline of Ca2+-ATPase activity and the increase of Ca2+ release channel activity should result in a down-regulation of Ca2+ dynamic uptake and an up-regulation of Ca2+ release induced by exposing the sarcoplasmic reticulum to a 0.4 mT, 50 Hz power frequency magnetic field.

Animals ; Calcium ; metabolism ; Calcium Signaling ; Electromagnetic Fields ; Muscle, Skeletal ; metabolism ; Rabbits ; Sarcoplasmic Reticulum ; metabolism ; radiation effects