• 제목/요약/키워드: Calcium entry

검색결과 58건 처리시간 0.024초

Ca2+-regulated ion channels

  • Cox, Daniel H.
    • BMB Reports
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    • 제44권10호
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    • pp.635-646
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    • 2011
  • Due to its high external and low internal concentration the $Ca^{2+}$ ion is used ubiquitously as an intracellular signaling molecule, and a great many $Ca^{2+}$-sensing proteins have evolved to receive and propagate $Ca^{2+}$ signals. Among them are ion channel proteins, whose $Ca^{2+}$ sensitivity allows internal $Ca^{2+}$ to influence the electrical activity of cell membranes and to feedback-inhibit further $Ca^{2+}$ entry into the cytoplasm. In this review I will describe what is understood about the $Ca^{2+}$ sensing mechanisms of the three best studied classes of $Ca^{2+}$-sensitive ion channels: Large-conductance $Ca^{2+}$-activated $K^+$ channels, small-conductance $Ca^{2+}$-activated $K^+$ channels, and voltage-gated $Ca^{2+}$ channels. Great strides in mechanistic understanding have be made for each of these channel types in just the past few years.

Ca2+ entry through reverse Na+/Ca2+ exchanger in NCI-H716, glucagon-like peptide-1 secreting cells

  • Choi, Kyung Jin;Hwang, Jin Wook;Kim, Se Hoon;Park, Hyung Seo
    • The Korean Journal of Physiology and Pharmacology
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    • 제26권3호
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    • pp.219-225
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    • 2022
  • Glucagon like peptide-1 (GLP-1) released from enteroendocine L-cells in the intestine has incretin effects due to its ability to amplify glucose-dependent insulin secretion. Promotion of an endogenous release of GLP-1 is one of therapeutic targets for type 2 diabetes mellitus. Although the secretion of GLP-1 in response to nutrient or neural stimuli can be triggered by cytosolic Ca2+ elevation, the stimulus-secretion pathway is not completely understood yet. Therefore, the aim of this study was to investigate the role of reverse Na+/Ca2+ exchanger (rNCX) in Ca2+ entry induced by muscarinic stimulation in NCI-H716 cells, a human enteroendocrine GLP-1 secreting cell line. Intracellular Ca2+ was repetitively oscillated by the perfusion of carbamylcholine (CCh), a muscarinic agonist. The oscillation of cytosolic Ca2+ was ceased by substituting extracellular Na+ with Li+ or NMG+. KB-R7943, a specific rNCX blocker, completely diminished CCh-induced cytosolic Ca2+ oscillation. Type 1 Na+/Ca2+ exchanger (NCX1) proteins were expressed in NCI-H716 cells. These results suggest that rNCX might play a crucial role in Ca2+ entry induced by cholinergic stimulation in NCI-H716 cells, a GLP-1 secreting cell line.

Afatinib Mediates Autophagic Degradation of ORAI1, STIM1, and SERCA2, Which Inhibits Proliferation of Non-Small Cell Lung Cancer Cells

  • Kim, Mi Seong;Kim, So Hui;Yang, Sei-Hoon;Kim, Min Seuk
    • Tuberculosis and Respiratory Diseases
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    • 제85권2호
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    • pp.147-154
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    • 2022
  • Background: The expression of calcium signaling pathway molecules is altered in various carcinomas, which are related to the proliferation and altered characteristics of cancer cells. However, changes in calcium signaling in anti-cancer drug-resistant cells (bearing a T790M mutation in epidermal growth factor receptor [EGFR]) remain unclear. Methods: Afatinib-mediated changes in the level of store-operated Ca2+ entry (SOCE)-related proteins and intracellular Ca2+ level in non-small cell lung cancer cells with T790M mutation in the EGFR gene were analyzed using western blot and ratiometric assays, respectively. Afatinib-mediated autophagic flux was evaluated by measuring the cleavage of LC3B-II. Flow cytometry and cell proliferation assays were conducted to assess cell apoptosis and proliferation. Results: The levels of SOCE-mediating proteins (ORAI calcium release-activated calcium modulator 1 [ORAI1], stromal interaction molecule 1 [STIM1], and sarco/endoplasmic reticulum Ca2+ ATPase [SERCA2]) decreased after afatinib treatment in non-small cell lung cancer cells, whereas the levels of SOCE-related proteins did not change in gefitinib-resistant non-small cell lung cancer cells (PC-9/GR; bearing a T790M mutation in EGFR). Notably, the expression level of SOCE-related proteins in PC-9/GR cells was reduced also responding to afatinib in the absence of extracellular Ca2+. Moreover, extracellular Ca2+ influx through the SOCE was significantly reduced in PC-9 cells pre-treated with afatinib than in the control group. Additionally, afatinib was found to decrease the level of SOCE-related proteins through autophagic degradation, and the proliferation of PC-9GR cells was significantly inhibited by a lack of extracellular Ca2+. Conclusion: Extracellular Ca2+ plays important role in afatinib-mediated autophagic degradation of SOCE-related proteins in cells with T790M mutation in the EGFR gene and extracellular Ca2+ is essential for determining anti-cancer drug efficacy.

SKF96365 impedes spinal glutamatergic transmission-mediated neuropathic allodynia

  • Qiru Wang;Yang Zhang;Qiong Du;Xinjie Zhao;Wei Wang;Qing Zhai;Ming Xiang
    • The Korean Journal of Physiology and Pharmacology
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    • 제27권1호
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    • pp.39-48
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    • 2023
  • Spinal nerve injury causes mechanical allodynia and structural imbalance of neurotransmission, which were typically associated with calcium overload. Storeoperated calcium entry (SOCE) is considered crucial elements-mediating intracellular calcium homeostasis, ion channel activity, and synaptic plasticity. However, the underlying mechanism of SOCE in mediating neuronal transmitter release and synaptic transmission remains ambiguous in neuropathic pain. Neuropathic rats were operated by spinal nerve ligations. Neurotransmissions were assessed by whole-cell recording in substantia gelatinosa. Immunofluorescence staining of STIM1 with neuronal and glial biomarkers in the spinal dorsal horn. The endoplasmic reticulum stress level was estimated from qRT-PCR. Intrathecal injection of SOCE antagonist SKF96365 dose-dependently alleviated mechanical allodynia in ipsilateral hind paws of neuropathic rats with ED50 of 18 ㎍. Immunofluorescence staining demonstrated that STIM1 was specifically and significantly expressed in neurons but not astrocytes and microglia in the spinal dorsal horn. Bath application of SKF96365 inhibited enhanced miniature excitatory postsynaptic currents in a dosage-dependent manner without affecting miniature inhibitory postsynaptic currents. Mal-adaption of SOCE was commonly related to endoplasmic reticulum (ER) stress in the central nervous system. SKF96365 markedly suppressed ER stress levels by alleviating mRNA expression of C/ EBP homologous protein and heat shock protein 70 in neuropathic rats. Our findings suggested that nerve injury might promote SOCE-mediated calcium levels, resulting in long-term imbalance of spinal synaptic transmission and behavioral sensitization, SKF96365 produces antinociception by alleviating glutamatergic transmission and ER stress. This work demonstrated the involvement of SOCE in neuropathic pain, implying that SOCE might be a potential target for pain management.

Ginsenosides Decrease β-Amyloid Production via Potentiating Capacitative Calcium Entry

  • Yoon Young Cho;Jeong Hill Park;Jung Hee Lee;Sungkwon Chung
    • Biomolecules & Therapeutics
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    • 제32권3호
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    • pp.301-308
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    • 2024
  • Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder characterized by extracellular amyloid plaques composed of amyloid β-peptide (Aβ). Studies have indicated that Ca2+ dysregulation is involved in AD pathology. It is reported that decreased capacitative Ca2+ entry (CCE), a refilling mechanism of intracellular Ca2+, resulting in increased Aβ production. In contrast, constitutive activation of CCE could decrease Aβ production. Panax ginseng Meyer is known to enhance memory and cognitive functions in healthy human subjects. We have previously reported that some ginsenosides decrease Aβ levels in cultured primary neurons and AD mouse model brains. However, mechanisms involved in the Aβ-lowering effect of ginsenosides remain unclear. In this study, we investigated the relationship between CCE and Aβ production by examining the effects of various ginsenosides on CCE levels. Aβ-lowering ginsenosides such as Rk1, Rg5, and Rg3 potentiated CCE. In contrast, ginsenosides without Aβ-lowering effects (Re and Rb2) failed to potentiate CCE. The potentiating effect of ginsenosides on CCE was inhibited by the presence of 2-aminoethoxydiphenyl borate (2APB), an inhibitor of CCE. 2APB alone increased Aβ42 production. Furthermore, the presence of 2APB prevented the effects of ginsenosides on Aβ42 production. Our results indicate that ginsenosides decrease Aβ production via potentiating CCE levels, confirming a close relationship between CCE levels and Aβ production. Since CCE levels are closely related to Aβ production, modulating CCE could be a novel target for AD therapeutics.

Alteration in Magnesium Level in Acute Myocardial Infarction

  • T. Angeline;K. Ramadevi;Aruna, Rita-Mary;G. Mohan;Nirmala Jeyaraj
    • Animal cells and systems
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    • 제7권2호
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    • pp.169-171
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    • 2003
  • Sodium, potassium, calcium, zinc and magnesium levels in the serum of 31 patients diagnosed as acute myocardial infarction were analyzed on admission (within 24 Hours) and after 48 hours. The results were compared with those of 26 age matched controls. No significant difference was observed in the mean sodium, potassium, calcium and zinc levels between the cases and controls. Compared to the controls, however, the variation in the level of magnesium is highly significant at the time of admission as well as after 48 hours. When the risk factors like diabetes mellitus, hypertension, smoking and alcohol were considered, it is found that there is no significant difference between the risk groups as well as between the patients. The alteration in magnesium level in acute myocardial infarction is independent of these risk factors. Within the first 24 hours, the significant decrease in serum magnesium (35-51% fall when compared with the control group), correlates with its entry into the cell following ischemia. From this hypomagnesemic state, it rises to 9-22 times after 48 hours. This hyper-magnesemia after 45 hours is probably due to the shift of magnesuim from the intracellular fluid compartment to the extracellular fluid compartment that follows cellular recovery. Therefore, including magnesium in the immediate management of acute myocardial infarction will be beneficial in the early recovery.

실험적(實驗的) 뇌허혈(腦虛血) 및 저산소증(低酸素症)에 대한 Flunarizine의 약효(藥效) -뇌장해에 대한 Flunarizine 효능- (Effect of Flunarizine on Experimental Ischemia and Hypoxia in Rats and Mice)

  • 김은미;김영진;신정희;윤재순
    • 약학회지
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    • 제32권5호
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    • pp.343-350
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    • 1988
  • Recent hypothesis suggested that intracellular accumulation of calcium is a common denominator of ischemic celullar damage. Flunarizine, a calcium entry blocker, posses vasodilating properties in cerebral vascular beds and clinically used in circulatory disorders. The present study was designed to evaluate the effect of flunarizine on ischemic and hypoxic brain damage. An ischemic model was made by bilateral carotid artery ligation (BCAL) in Wistar strain rat. Hypoxic model was made by intravenous injection(i.v.) of KCN to rats and mice. In mice, flunarizine not only reduced the mortality of KCN, but also delayed the onset time of convulsion. The contents of ATP, creatine phosphate and glucose, cerebral energy metabolite, decreased 30 minutes after BCAL and KCN i, v, while that of lactate increased. But these variations were suppressed by flunarizine. Furthermore, increase in the dosage of flunarizne generally promoted the recovery of cerebral energy metabolites in hypoxic animals. The results suggest that flunarizine had a protective effect against ischemic and hypoxic brain damage due to its ameliorating action on the cerebral energy metabolism.

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Flos magnoliae constituent fargesin has an anti-allergic effect via ORAI1 channel inhibition

  • Hong, Phan Thi Lam;Kim, Hyun Jong;Kim, Woo Kyung;Nam, Joo Hyun
    • The Korean Journal of Physiology and Pharmacology
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    • 제25권3호
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    • pp.251-258
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    • 2021
  • Flos magnoliae (FM), the dry flower buds of Magnolia officinalis or its related species, is a traditional herbal medicine commonly used in Asia for symptomatic relief of and treating allergic rhinitis, headache, and sinusitis. Although several studies have reported the effects of FM on store-operated calcium entry (SOCE) via the ORAI1 channel, which is essential during intracellular calcium signaling cascade generation for T cell activation and mast cell degranulation, the effects of its isolated constituents on SOCE remain unidentified. Therefore, we investigated which of the five major constituents of 30% ethanoic FM (vanillic acid, tiliroside, eudesmin, magnolin, and fargesin) inhibit SOCE and their physiological effects on immune cells. The conventional whole-cell patch clamp results showed that fargesin, magnolin, and eudesmin significantly inhibited SOCE and thus human primary CD4+ T lymphocyte proliferation, as well as allergen-induced histamine release in mast cells. Among them, fargesin demonstrated the most potent inhibitory effects not only on ORAI1 (IC50 = 12.46 ± 1.300 μM) but also on T-cell proliferation (by 87.74% ± 1.835%) and mast cell degranulation (by 20.11% ± 5.366%) at 100 μM. Our findings suggest that fargesin can be a promising candidate for the development of therapeutic drugs to treat allergic diseases.

Homer2 regulates amylase secretion via physiological calcium oscillations in mouse parotid gland acinar cells

  • Kang, Namju;Kang, Jung Yun;Shin, Dong Min;Yang, Yu-Mi
    • International Journal of Oral Biology
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    • 제45권2호
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    • pp.58-63
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    • 2020
  • The salivary glands secrete saliva, which plays a role in the maintenance of a healthy oral environment. Under physiological conditions, saliva secretion within the acinar cells of the gland is regulated by stimulation of specific calcium (Ca2+) signaling mechanisms such as increases in the intracellular Ca2+ concentration ([Ca2+]i) via storeoperated Ca2+ entry, which involves components such as Orai1, transient receptor potential (TRP) canonical 1, stromal interaction molecules, and inositol 1,4,5-triphosphate (IP3) receptors (IP3Rs). Homer proteins are scaffold proteins that bind to G protein-coupled receptors, IP3Rs, ryanodine receptors, and TRP channels. However, their exact role in Ca2+ signaling in the salivary glands remains unknown. In the present study, we investigated the role of Homer2 in Ca2+ signaling and saliva secretion in parotid gland acinar cells under physiological conditions. Deletion of Homer2 (Homer2-/-) markedly decreased the amplitude of [Ca2+]i oscillations via the stimulation of carbachol, which is physiologically concentrated in parotid acinar cells, whereas the frequency of [Ca2+]i oscillations showed no difference between wild-type and Homer2-/- mice. Homer2-/- mice also showed a significant decrease in amylase release by carbachol in the parotid gland in a dose-dependent manner. These results suggest that Homer2 plays a critical role in maintaining [Ca2+]i concentration and secretion of saliva in mouse parotid gland acinar cells.

2급 치근이개부 병변의 합성골 이식 시 혈소판 농축 혈장의 재생에 관한 효과 (The Regeneration Effect of Platelet-Rich Plasma on the Treatment of Grade II Furcation Involvement Using Synthetic Bone in Human)

  • 김준희;임성빈;정진형
    • Journal of Periodontal and Implant Science
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    • 제31권2호
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    • pp.477-488
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    • 2001
  • The present study evaluated of regeneration effect of platelet rich plasma on the treatment of grade II furcation involvement, with coralline calcium phosphate bone in humans. 30 teeth with grade II furcation defect were selected and 15 teeth(control) were treated with coralline calcium phosphate bone, the others(test) were treated with coralline calcium phosphate bone and platelet rich plasma. Pocket depth, clinical attachment level, width of keratinized gingiva width were measured at baseline, postoperative 3, 6months. from cementoenamel junction to alveolar crest and fundus were measured at baseline, 6months(re-entry). Both groups were statistically analyzed by Wilcoxon signed Ranks Test & Mann-whitney Test using SPSS program(5% significance level). The results were as follows: 1. Pocket depth, clinical attachment level, keratinized gingva width, cementoenamel junction - alveolar crest, cementoenamel junction - fundus were not differ significantly in both groups at baseline 2. The change of pocket depth, clinical attachment level, keratinized gingva width, cementoenamel junction - alveolar crest, cementoenamel junction - fundus in both groups were decreased significantly at 3, 6months(p<0.05). 3. The change of pocket depth, clinical attachment level in test group decreased significantly than control at 3, 6months(p<0.05). 4. The change of keratinized gingiva width, cementoenamel junctional - alveolar crest, cementoenamel junction - fundus were not differ significantly in both groups at 3, 6months. 5. The pocket depth, clinical attachment level, keratinized gingiva width exhibited marked changes at 3 months in both groups. In conclusion, the results of this study suggest that platelet rich plasma have adjunctive clinical treatment effect to periodontal regeneration in grade II furcation defects.

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