Cell calcium最新文献_第5页

NAADP-mediated calcium release promotes angiopoietin 2 secretion by regulating Rab46-dependent Weibel-Palade body trafficking naadp介导的钙释放通过调节rab46依赖性Weibel-Palade体运输促进血管生成素2的分泌

IF 4 2区生物学 Q2 CELL BIOLOGY

Cell calcium

Pub Date : 2025-11-01 Epub Date: 2025-08-14 DOI: 10.1016/j.ceca.2025.103068

Ryan D. Murray , Melissa Rose , Katarina T. Miteva , David J. Beech , Lynn McKeown

Angiopoietin2 (Ang2), a regulator of angiogenesis, is stored with other pro-inflammatory and pro-thrombotic mediators, in endothelial-specific vesicles called Weibel-Palade bodies (WPBs). Acute stimulation of endothelial cells with histamine, delays Ang2 secretion by activating Rab46-specific trafficking of Ang2-containing WPBs to the microtubule organising centre (MTOC), where they persist until Ca²⁺ binds to the EF-hand of Rab46, enabling detachment. Here, using Ca²⁺ imaging and high-resolution light microscopy, we pharmacologically investigated the contribution of endolysosomal two-pore channel proteins (TPC) to the Ca²⁺ signal necessary for WPB detachment and Ang2 secretion. We show an increase in the histamine-evoked clustering of Rab46 (and thus WPBs) at the MTOC in the presence of TPC inhibitors Ned-19 and tetrandrine, and a decrease in the presence of a TPC2 agonist, TPC2-A1-N. Histamine-evoked secretion of Ang2 was decreased by pharmacological inhibition of TPC channels but potentiated in the presence of TPC2-A1-N. These data suggest that histamine-mediated Ca²⁺ release via TPC2 channels is necessary for the Rab46-dependent detachment of Ang2-positive WPBs from the MTOC and thus Ang2 secretion.

Summary

Ca²⁺ binding to the EF-hand of Rab46 in endothelial cells has previously been reported but the molecular mechanisms and functional relevance are unclear. Here, the authors show that Ca²⁺ released from TPC channels regulates the detachment of Rab46-positive WPBs from the MTOC, which thereby promotes secretion of Ang2.

血管生成素2 （Ang2）是一种血管生成调节剂，与其他促炎和促血栓介质一起储存在内皮特异性囊泡中，称为韦贝尔-帕拉德小体（WPBs）。用组胺急性刺激内皮细胞，通过激活含有Ang2的WPBs到微管组织中心（MTOC）的Rab46特异性运输，延迟Ang2的分泌，在那里它们持续存在，直到Ca 2 +与Rab46的EF-hand结合，使其脱离。在这里，我们使用Ca 2 +成像和高分辨率光学显微镜，从药理学上研究了内溶酶体两孔通道蛋白（TPC）对WPB脱离和Ang2分泌所必需的Ca 2 +信号的贡献。我们发现，在TPC2抑制剂Ned-19和粉防己碱存在的情况下，MTOC处组胺诱发的Rab46聚类（以及WPBs）增加，而TPC2激动剂TPC2- a1 - n存在的情况下，组胺诱发的Rab46聚类（以及WPBs）减少。组胺诱发的Ang2分泌因药物抑制TPC通道而减少，但在TPC2-A1-N存在时增强。这些数据表明，组胺介导的Ca +通过TPC2通道释放是rab46依赖性的Ang2阳性WPBs脱离MTOC和Ang2分泌所必需的。ca 2 +在内皮细胞中与Rab46的EF-hand结合已有报道，但其分子机制和功能相关性尚不清楚。在这里，作者证明了从TPC通道释放的Ca 2 +可以调节rab46阳性WPBs从MTOC上脱离，从而促进Ang2的分泌。

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引用次数: 0

Abnormal calcium activity and CREB phosphorylation are associated with motor memory impairment in presenilin-1 mutant knock-in mice 早老素-1突变敲入小鼠的异常钙活性和CREB磷酸化与运动记忆障碍有关

IF 4.3 2区生物学 Q2 CELL BIOLOGY

Cell calcium

Pub Date : 2025-09-01 Epub Date: 2025-07-02 DOI: 10.1016/j.ceca.2025.103048

Yuan Lin , Yang Bai , Alejandro Martin-Avila , Wei Li , Xujun Wu , Edward Ziff , Wen-Biao Gan

Introduction

Presenilin (PS) gene mutations cause memory impairment in early-onset familial Alzheimer’s disease (FAD), but the underlying mechanisms remain unclear.

Methods

We examined the effects of the PS1 M146V FAD mutation on motor learning, motor learning-related changes in neuronal Ca²⁺activity and CREB phosphorylation in the primary motor cortex.

Results

We found that PS1 M146V knock-in mice displayed long-term deficiencies in motor skill learning. Ca²⁺ levels are altered in a cortical layer and neuron type-specific manner in PS1 mutant mice as compared to WT control mice. Notably, while running caused a significant increase of CREB phosphorylation in WT mice, it led to a significant decrease of CREB phosphorylation in layer 5 neurons of mutant mice.

Discussion

These findings suggest that alterations of Ca²⁺ activity and CREB phosphorylation in deep cortical layers are early events leading to memory impairment in the PS1 mutation-related familial form of AD.

早老素（PS）基因突变导致早发性家族性阿尔茨海默病（FAD）的记忆障碍，但其潜在机制尚不清楚。方法我们检测了PS1 M146V FAD突变对运动学习、运动学习相关的神经元Ca2+活性变化和初级运动皮层CREB磷酸化的影响。结果我们发现PS1 M146V敲入小鼠在运动技能学习方面表现出长期缺陷。与WT对照小鼠相比，PS1突变小鼠的Ca2+水平在皮质层和神经元类型特异性方式上发生改变。值得注意的是，虽然跑步导致WT小鼠CREB磷酸化显著增加，但却导致突变小鼠第5层神经元CREB磷酸化显著降低。这些发现表明，在PS1突变相关的家族性AD中，深层皮质层Ca2+活性和CREB磷酸化的改变是导致记忆障碍的早期事件。

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引用次数: 0

Calcium at the crossroads: TPC2’s role in LRRK2-linked Parkinson’s disease 十字路口的钙：TPC2在lrrk2相关帕金森病中的作用

IF 4.3 2区生物学 Q2 CELL BIOLOGY

Cell calcium

Pub Date : 2025-09-01 Epub Date: 2025-06-17 DOI: 10.1016/j.ceca.2025.103049

Federica De Lazzari , Simone Wanderoy , Alexander J Whitworth

The pathogenic mechanisms of LRRK2 are hotly debated but regulation of lysosomal homeostasis has emerged as a leading focus area. In recent work, Gregori et al. show that Ca²⁺ release through the lysosomal Two-Pore Channel 2 (TPC2) could be a significant contributor to dopaminergic neuron vulnerability.

LRRK2的致病机制一直备受争议，但对溶酶体稳态的调节已成为一个主要的焦点领域。在最近的工作中，Gregori等人表明，通过溶酶体双孔通道2 （TPC2）释放Ca2+可能是多巴胺能神经元易感性的一个重要因素。

引用次数: 0

VDAC1 as Janus in cell death and survival: Annexin A5 to the rescue VDAC1在细胞死亡和存活中起Janus作用，膜联蛋白A5起拯救作用

IF 4.3 2区生物学 Q2 CELL BIOLOGY

Cell calcium

Pub Date : 2025-09-01 Epub Date: 2025-07-03 DOI: 10.1016/j.ceca.2025.103052

Ophélie Champion , Jacek J. Litewka , Pawel E. Ferdek , Geert Bultynck

VDAC1, a large conductance channel in the outer mitochondrial membrane, plays a crucial role in mitochondrial physiology. VDAC1 supports cellular metabolism and survival by serving as a mitochondrial Ca²⁺-uptake and ATP-exit system. Conversely, VDAC1 also contributes to apoptosis by forming oligomeric pores mediating cytochrome c release. Recently, Oflaz et al., EMBO J, 2025, identified the Ca²⁺-binding protein Annexin A5 as a dynamic, Ca²⁺-dependent switch that enhances VDAC1’s Ca²⁺-transport function while at the same time preventing pro-apoptotic VDAC1 oligomer formation.

VDAC1是线粒体外膜上的一个大电导通道，在线粒体生理中起着至关重要的作用。VDAC1通过作为线粒体Ca2+摄取和atp退出系统支持细胞代谢和存活。相反，VDAC1也通过形成低聚孔介导细胞色素c的释放来促进细胞凋亡。最近，Oflaz等人，EMBO J， 2025发现Ca2+结合蛋白Annexin A5是一种动态的Ca2+依赖性开关，可增强VDAC1的Ca2+转运功能，同时阻止促凋亡VDAC1寡聚物的形成。

引用次数: 0

Macrophage migration inhibitory factor induces phospholamban phosphorylation in cardiac muscle 巨噬细胞迁移抑制因子诱导心肌磷酸化

IF 4.3 2区生物学 Q2 CELL BIOLOGY

Cell calcium

Pub Date : 2025-09-01 Epub Date: 2025-07-04 DOI: 10.1016/j.ceca.2025.103051

Zihan Tang , Feng Liu , Miyuki Nishi , Fabienne Mackay , Mutsuo Harada , Hiroshi Takeshima

The pleiotropic cytokine macrophage migration inhibitory factor (MIF) elevates sarcoplasmic reticulum (SR) Ca²⁺ content and enhances Ca²⁺ transient in cardiac muscle. Our imaging and immunoblot data indicated that the MIF-evoked effect is caused mainly by the phosphorylation of the SR Ca²⁺-pump regulator phospholamban (PLN). Gene expression data suggested that the cluster of differentiation 74 (CD74) and the C-X-C motif chemokine receptor 7 (CXCR7) form a major MIF receptor complex in cardiomyocytes, but CXCR7 activation alone seemed sufficient to exert the MIF-evoked effect. Our pharmacological assessments suggested that phosphoinositide 3-kinase (PI3K), AKT kinase and endothelial nitric oxide synthase (eNOS) were continuously stimulated in the downstream of CXCR7 activation. Furthermore, NO thus generated likely reacted to activate Ca²⁺/calmodulin-dependent protein kinase II (CaMKII), leading to PLN phosphorylation and subsequent SR Ca²⁺-pump activation. Therefore, the CXCR7-PI3K-AKT-eNOS-CaMKII-PLN axis is proposed as a central pathway for MIF-evoked potentiation of cardiac Ca²⁺ signaling.

多受体细胞因子巨噬细胞迁移抑制因子（MIF）可提高肌浆网（SR） Ca2+含量，增强心肌Ca2+瞬态。我们的成像和免疫印迹数据表明，mif诱发的效应主要是由SR Ca2+泵调节因子磷蛋白（PLN）的磷酸化引起的。基因表达数据表明，分化簇74 （CD74）和C-X-C基序趋化因子受体7 （CXCR7）在心肌细胞中形成了一个主要的MIF受体复合物，但单独激活CXCR7似乎足以发挥MIF诱发的作用。我们的药理学评估表明，在CXCR7激活的下游，磷酸肌肽3激酶（PI3K）、AKT激酶和内皮型一氧化氮合酶（eNOS）持续受到刺激。此外，由此产生的NO可能反应激活Ca2+/钙调素依赖性蛋白激酶II (CaMKII)，导致PLN磷酸化和随后的SR Ca2+泵激活。因此，CXCR7-PI3K-AKT-eNOS-CaMKII-PLN轴被认为是mif诱发心脏Ca2+信号增强的中心途径。

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引用次数: 0

GAT3-dependent regulation of glioma invasiveness via a lipid raft-associated PMCA4 Ca2+ transporter and a downstream CaMKII/CREB signaling – implications for compartmentalized signaling in glioma tumors 通过脂质筏相关的PMCA4 Ca2+转运体和下游CaMKII/CREB信号传导对胶质瘤侵袭性的gat3依赖性调节-对胶质瘤肿瘤区隔化信号传导的影响

IF 4.3 2区生物学 Q2 CELL BIOLOGY

Cell calcium

Pub Date : 2025-09-01 Epub Date: 2025-06-19 DOI: 10.1016/j.ceca.2025.103050

Marta Sobolczyk-Prawda , Agnieszka Kapsa , Malwina Lisek , Julia Tomczak , Katarzyna Sobierajska , Maciej Radek , Feng Guo , Tomasz Boczek

Emerging evidence underscores the crucial role of compartmentalized Ca²⁺ and GABA signaling in the development and progression of gliomas. Our findings reveal that low GAT3 expression and high PMCA4 levels are strongly associated with poor survival outcomes in glioma patients, suggesting their involvement in tumor progression. Using C6 glioma model, we uncovered a dynamic interaction between GAT3 and PMCA4 within lipid raft microdomains, which plays a key role in fine-tuning of localized Ca²⁺ dynamics in response to GABA stimulation. Knockdown of PMCA4 increased resting Ca²⁺concentration and enhanced Ca²⁺ accumulation in lipid rafts following 3-min pulse GABA stimulation, significantly impairing glioma cell migration and invasion. Interestingly, the expression of Ca²⁺ chelator parvalbumin in rafts abolished both baseline and GABA-stimulated Ca²⁺ rises, effectively restoring the migratory and invasive potential of tumor cells. We further demonstrated that GAT3 interacted with calmodulin, a pivotal regulator of PMCA4, and this interaction was decreased following 24 h GABA treatment. Long-term GABA stimulation also disrupted PMCA4/GAT3 complex, overloaded lipid rafts with Ca²⁺ and decreased glioma invasiveness in the presence of PMCA4. In these conditions, we observed GAT3- and Ca²⁺/calmodulin-dependent protein kinase II-dependent CREB phosphorylation at Ser133, which was controlled by Ca²⁺ events in lipid rafts and required to maintain glioma invasiveness. Our study uncovers a previously unrecognized GAT3-dependent mechanism of Ca²⁺compartmentalization in membrane microdomains, shedding new light on its potential role in tumor behavior. Understanding these local Ca²⁺ signaling partnerships will offer valuable insights into gliomagenesis and could lead to the development of novel therapeutic strategies for glioma treatment.

新出现的证据强调了区隔化Ca 2 +和GABA信号在胶质瘤发生和发展中的关键作用。我们的研究结果表明，低GAT3表达和高PMCA4水平与胶质瘤患者的不良生存结果密切相关，表明它们参与肿瘤进展。利用C6胶质瘤模型，我们发现了脂筏微域内GAT3和PMCA4之间的动态相互作用，这在GABA刺激下局部Ca2+动力学的微调中起关键作用。在3分钟脉冲GABA刺激后，PMCA4的下调增加了静息Ca2+浓度，增强了脂筏中Ca2+的积累，显著损害了胶质瘤细胞的迁移和侵袭。有趣的是，筏中Ca2+螯合剂小白蛋白的表达消除了基线和gaba刺激的Ca2+升高，有效地恢复了肿瘤细胞的迁移和侵袭潜力。我们进一步证明GAT3与钙调蛋白相互作用，钙调蛋白是PMCA4的关键调节因子，并且这种相互作用在24小时的GABA处理后减少。长期GABA刺激也会破坏PMCA4/GAT3复合物，超载Ca2+脂筏，并降低PMCA4存在时胶质瘤的侵袭性。在这些条件下，我们观察到GAT3-和Ca2+/钙调素依赖性蛋白激酶ii依赖性CREB的Ser133磷酸化，这是由脂筏中的Ca2+事件控制的，是维持胶质瘤侵袭性所必需的。我们的研究揭示了一种以前未被认识的膜微域中Ca2+区隔化的gat3依赖机制，为其在肿瘤行为中的潜在作用提供了新的视角。了解这些局部Ca 2 +信号伙伴关系将为胶质瘤发生提供有价值的见解，并可能导致胶质瘤治疗新治疗策略的开发。

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引用次数: 0

Copine A is essential for calcium homeostasis in Dictyostelium 铜碱A对盘基骨菌的钙稳态至关重要

IF 4.3 2区生物学 Q2 CELL BIOLOGY

Cell calcium

Pub Date : 2025-09-01 Epub Date: 2025-07-16 DOI: 10.1016/j.ceca.2025.103055

Amber D. Ide , Cody T. Morrison , Christer A. Carne , Cynthia K. Damer

Copines are a family of calcium-dependent phospholipid-binding proteins found in most eukaryotic organisms. The expression of multiple copine genes is dysregulated in various types of human cancers. Yet, a common mechanistic function for copines remains enigmatic. We are studying copines in Dictyostelium, which has six copine genes (cpnA-cpnF). Cells lacking cpnA (cpnA-) exhibit many phenotypes including defects in development, chemotaxis, adhesion, and contractile vacuole (CV) function. In this study, we identified a novel link between CpnA and calcium homeostasis. We found that cpnA- cells have more phosphatidylserine (PS) exposed in the outer leaflet of the plasma membrane due to having an increased intracellular calcium concentration. The PS exposure defect and the enlarged CV defect in cpnA- cells were rescued by chelating calcium. We further investigated the role of PatA, a CV-localized Ca²⁺-ATPase responsible for pumping calcium into the CV. Although cpnA- cells expressed normal levels of patA, immunofluorescence revealed reduced PatA localization to the CV membrane. Notably, patA knockdown (patA^KD) cells phenocopied cpnA- cells, displaying enlarged CVs, elevated intracellular calcium, and increased PS exposure. Taken together, our findings suggest that CpnA promotes calcium sequestration into the CV, likely by regulating PatA localization or activity. This role in calcium homeostasis provides a mechanistic framework for understanding copine function and offers insight into how calcium dysregulation associated with copines may contribute to cancer progression.

Copines是在大多数真核生物中发现的钙依赖性磷脂结合蛋白家族。多种copine基因的表达在各种类型的人类癌症中失调。然而，复制体的共同机制功能仍然是个谜。我们正在研究Dictyostelium中含有6个copine基因（cpnA-cpnF）的copine。缺乏cpnA （cpnA-）的细胞表现出多种表型，包括发育、趋化性、粘附和收缩液泡（CV）功能缺陷。在这项研究中，我们发现了CpnA和钙稳态之间的一种新的联系。我们发现由于胞内钙浓度的增加，cpnA-细胞有更多的磷脂酰丝氨酸（PS）暴露在质膜外小叶中。螯合钙修复了cpnA-细胞的PS暴露缺陷和CV增大缺陷。我们进一步研究了PatA的作用，PatA是一种位于CV的Ca 2 + - atp酶，负责将钙泵入CV。虽然cpnA-细胞表达正常水平的patA，但免疫荧光显示patA在CV膜上的定位减少。值得注意的是，patA敲低（patAKD）细胞表型化cpnA-细胞，表现为CVs增大、细胞内钙升高和PS暴露增加。综上所述，我们的研究结果表明，CpnA可能通过调节PatA的定位或活性来促进钙在CV中的固存。这种在钙稳态中的作用为理解copine的功能提供了一个机制框架，并为了解与copine相关的钙失调如何促进癌症进展提供了见解。

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引用次数: 0

Paclitaxel activates SOCE/ICRAC in dorsal root ganglion neurons: implications for paclitaxel-induced peripheral neuropathy 紫杉醇激活背根神经节神经元的SOCE/ICRAC：紫杉醇诱导的周围神经病变的意义

IF 4.3 2区生物学 Q2 CELL BIOLOGY

Cell calcium

Pub Date : 2025-09-01 Epub Date: 2025-05-27 DOI: 10.1016/j.ceca.2025.103040

Marta Delconti , Tiziana Ravasenga , Marianna Dionisi , Tiziana Romanazzi , Fausto Chiazza , Silvia Giatti , Dmitry Lim , Armando A. Genazzani , Beatrice Riva , Cristina Meregalli , Guido Cavaletti , Carla Distasi

Paclitaxel (PTX) is one of the most widely used antineoplastic drugs for the treatment of solid cancers. Its mechanism of action involves binding to β-tubulin subunits, leading to the stabilization of microtubule polymers and subsequent cell cycle arrest. Despite its efficacy, PTX is associated with significant adverse effects, most notably peripheral neurotoxicity and neuropathic pain, which represent the primary dose-limiting side effects. In sensory neurons, PTX affects multiple molecular pathways, with early alterations in excitability and calcium signaling following acute drug exposure. To investigate these mechanisms, we employed a combination of calcium imaging, electrophysiological techniques, and pharmacological approaches to explore the role of ORAI channels in the excitability and calcium dynamics of mouse dorsal root ganglion neurons. Our findings reveal that acute exposure to low doses of PTX triggers IP₃-dependent calcium release and activates a store-operated calcium entry through STIM-ORAI dependent I_CRAC. Moreover, acute PTX application induced the activation of a sustained calcium inward current, V_m depolarization and triggered action potential firing that was strongly attenuated by I_CRAC inhibition. Molecular analyses further revealed a significant upregulation of Orai1, Orai2, and Stim2 mRNA levels, accompanied by elevated ORAI1 protein expression, in a rat model of paclitaxel-induced peripheral neuropathy. These results suggest that ORAI and STIM proteins represent promising molecular targets for developing therapies aimed at mitigating the side effects of PTX.

紫杉醇（Paclitaxel， PTX）是目前应用最广泛的治疗实体肿瘤的抗肿瘤药物之一。其作用机制包括与β-微管蛋白亚基结合，导致微管聚合物的稳定和随后的细胞周期阻滞。尽管其疗效良好，但PTX也有明显的不良反应，最明显的是周围神经毒性和神经性疼痛，这是主要的剂量限制性副作用。在感觉神经元中，PTX影响多种分子通路，在急性药物暴露后早期改变兴奋性和钙信号。为了研究这些机制，我们采用钙成像、电生理技术和药理学方法相结合的方法来探索ORAI通道在小鼠背根神经节神经元的兴奋性和钙动力学中的作用。我们的研究结果表明，急性暴露于低剂量的PTX会触发ip3依赖性钙释放，并通过STIM-ORAI依赖性ICRAC激活储存操作的钙进入。此外，急性PTX应用诱导持续钙向内电流的激活，Vm去极化和触发动作电位放电，这被ICRAC抑制强烈减弱。分子分析进一步显示，在紫杉醇诱导的大鼠周围神经病变模型中，Orai1、Orai2和Stim2 mRNA水平显著上调，同时Orai1蛋白表达升高。这些结果表明，ORAI和STIM蛋白是开发旨在减轻PTX副作用的治疗方法的有希望的分子靶点。

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引用次数: 0

Dietary calcium intake controls epithelial expression of TRPV6 independent of 1,25(OH)2D3 endocrine signaling 膳食钙摄入控制不依赖于1,25(OH)2D3内分泌信号的TRPV6上皮表达

IF 4.3 2区生物学 Q2 CELL BIOLOGY

Cell calcium

Pub Date : 2025-09-01 Epub Date: 2025-07-05 DOI: 10.1016/j.ceca.2025.103053

Hinata Tanishige , Atsushi Uekawa , Hitoki Yamanaka , Shigeaki Kato , Ritsuko Masuyama

Dietary calcium intake modifies the action of active vitamin D [1,25(OH)₂D₃], which promotes the expression of transient receptor potential vanilloid (TRPV) 6, an epithelial calcium channel, to initiate intestinal calcium absorption in response to biological requirements. However, it is unclear whether the change caused by dietary intake results from endocrine regulation or the direct responses to luminal contents. In this study, to reveal the underlying mechanisms of intestinal calcium transport in response to dietary intake, we assessed the early postprandial responses in mice.

Although mice lacking intestinal vitamin D receptor function (Int Vdr-) exhibited severe calcium deficiency, a high-calcium diet (1 % calcium) containing 2-fold calcium compared to a control diet reversed impaired calcium absorption and compensated for the mechanisms of 1,25(OH)₂D₃-dependent transcellular calcium transport. Additionally, the calcium-sensing receptor (CaSR) was abundantly present at the basolateral site in the intestine and the signals were emphasized by a high-calcium diet.

To examine the direct response of intestinal epithelium to dietary intake, wild-type (Int Vdr+) and Int Vdr- mice were fed a control or high-calcium diet for 30- or 60-min after 23 h fasting. Serum glucose levels increased 30 min post-feeding in either genotype. TRPV6 expression increased 30 min post-feeding, whereas serum calcium levels were unaltered, suggesting that dietary intake stimulates TRPV6 expression.

These data suggest that the regulation of calcium absorption activated immediately after feeding differs from the mechanism involving endocrine responses. Factors altered in the early phase of feeding, such as glucose, may contribute to the regulation of calcium absorption.

膳食钙摄入改变活性维生素D的作用[1,25(OH)2D3]，促进上皮钙通道瞬时受体电位香兰素（TRPV） 6的表达，以响应生物需求启动肠道钙吸收。然而，目前尚不清楚饮食摄入引起的变化是由内分泌调节引起的，还是对肠管含量的直接反应。在这项研究中，为了揭示肠道钙转运对饮食摄入的潜在机制，我们评估了小鼠餐后的早期反应。尽管缺乏肠道维生素D受体功能（Int Vdr-）的小鼠表现出严重的钙缺乏症，但与对照饮食相比，含钙2倍的高钙饮食（1%钙）逆转了受损的钙吸收，并补偿了依赖1,25(OH) 2d3的跨细胞钙转运机制。此外，钙敏感受体（CaSR）大量存在于肠的基底外侧，高钙饮食强调了信号。为了研究肠道上皮对膳食摄入的直接反应，野生型（Int Vdr+）和Int Vdr-小鼠在禁食23小时后分别饲喂对照或高钙饮食30分钟或60分钟。两种基因型的血清葡萄糖水平均在饲喂后30分钟升高。TRPV6表达在饲喂后30分钟增加，而血清钙水平不变，提示膳食摄入刺激TRPV6表达。这些数据表明，摄食后立即激活的钙吸收调节与涉及内分泌反应的机制不同。在喂养早期改变的因素，如葡萄糖，可能有助于钙吸收的调节。

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引用次数: 0

Calcium imaging: Unraveling the neurobiological mechanisms of depression across cellular and circuit dimensions 钙成像：揭示抑郁的神经生物学机制跨越细胞和电路维度

IF 4.3 2区生物学 Q2 CELL BIOLOGY

Cell calcium

Pub Date : 2025-09-01 Epub Date: 2025-07-08 DOI: 10.1016/j.ceca.2025.103054

Xu Han , Jinfang Song , Zihui Geng , Runxin Li , Bingjin Li

Calcium imaging has emerged as a pivotal technique for monitoring neuronal and glial activity, gaining widespread recognition in neuroscience research. This method primarily utilizes genetically encoded calcium indicators (GECIs) or synthetic fluorescent dyes to detect physiologically relevant calcium dynamics. Despite being one of the most prevalent mental disorders, depression's pathogenesis remains poorly understood. Calcium imaging serves as a powerful tool to identify depression-related cell types and neural circuits. This review systematically summarizes the evolution of calcium indicators and their integration with behavioral paradigms, electrophysiology, optogenetics, and chemogenetics to elucidate cellular and circuit mechanisms underlying depression. In addition, calcium imaging in depression and other disease comorbidities is also discussed. These synthesized findings establish a framework for developing precision-targeted antidepressant interventions.

钙成像已成为监测神经元和神经胶质活动的关键技术，在神经科学研究中获得广泛认可。该方法主要利用遗传编码钙指标（GECIs）或合成荧光染料来检测生理相关的钙动力学。尽管是最普遍的精神障碍之一，但抑郁症的发病机制仍然知之甚少。钙成像是识别抑郁症相关细胞类型和神经回路的有力工具。本文系统地综述了钙指标的演变及其与行为范式、电生理学、光遗传学和化学遗传学的结合，以阐明抑郁症的细胞和电路机制。此外，还讨论了钙显像在抑郁症和其他疾病合并症中的应用。这些综合发现为开发精确靶向的抗抑郁药物干预措施建立了框架。

引用次数: 0