Pub Date : 2025-01-01DOI: 10.1016/j.ceca.2024.102983
Rebecca Frank Hayward , Adam E. Cohen
Calcium mediates many important signals in dendrites. However, the basic transport properties of calcium in dendrites have been difficult to measure: how far and how fast does a local influx of calcium propagate? We developed an all-optical system for simultaneous targeted Ca2+ import and Ca2+ concentration mapping. We co-expressed a blue light-activated calcium selective channelrhodopsin, CapChR2, with a far-red calcium sensor, FR-GECO1c, in cultured rat hippocampal neurons, and used patterned optogenetic stimulation to introduce calcium into cells with user-defined patterns of space and time. We determined a mean steady-state length constant for Ca2+ transport ϕ ∼ 5.8 μm, a half-life for return to baseline t1/2 ∼ 1.7 s, and an effective diffusion coefficient D ∼ 20 μm2/s, though there were substantial differences in Ca2+ dynamics between proximal and distal dendrites. At high Ca2+ concentration, distal dendrites showed nonlinear activation of Ca2+ efflux, which we pharmacologically ascribed to the NCX1 antiporter. Genetically encoded tools for all-optical mapping of Ca2+ transport and handling provide a powerful capability for studying this important messenger.
{"title":"All-optical mapping of Ca2+ transport and homeostasis in dendrites","authors":"Rebecca Frank Hayward , Adam E. Cohen","doi":"10.1016/j.ceca.2024.102983","DOIUrl":"10.1016/j.ceca.2024.102983","url":null,"abstract":"<div><div>Calcium mediates many important signals in dendrites. However, the basic transport properties of calcium in dendrites have been difficult to measure: how far and how fast does a local influx of calcium propagate? We developed an all-optical system for simultaneous targeted Ca<sup>2+</sup> import and Ca<sup>2+</sup> concentration mapping. We co-expressed a blue light-activated calcium selective channelrhodopsin, CapChR2, with a far-red calcium sensor, FR-GECO1c, in cultured rat hippocampal neurons, and used patterned optogenetic stimulation to introduce calcium into cells with user-defined patterns of space and time. We determined a mean steady-state length constant for Ca<sup>2+</sup> transport <em>ϕ</em> ∼ 5.8 μm, a half-life for return to baseline <em>t</em><sub>1/2</sub> ∼ 1.7 s, and an effective diffusion coefficient <em>D</em> ∼ 20 μm<sup>2</sup>/s, though there were substantial differences in Ca<sup>2+</sup> dynamics between proximal and distal dendrites. At high Ca<sup>2+</sup> concentration, distal dendrites showed nonlinear activation of Ca<sup>2+</sup> efflux, which we pharmacologically ascribed to the NCX1 antiporter. Genetically encoded tools for all-optical mapping of Ca<sup>2+</sup> transport and handling provide a powerful capability for studying this important messenger.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"125 ","pages":"Article 102983"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11735331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.ceca.2024.102988
Julio C. Sánchez , Laura V. Muñoz , Barbara E. Ehrlich
{"title":"Corrigendum to “Modulating TRPV4 channels with paclitaxel and lithium” [Cell Calcium 91 (2020) 102266]","authors":"Julio C. Sánchez , Laura V. Muñoz , Barbara E. Ehrlich","doi":"10.1016/j.ceca.2024.102988","DOIUrl":"10.1016/j.ceca.2024.102988","url":null,"abstract":"","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"125 ","pages":"Article 102988"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.ceca.2024.102985
Xiao-Hua Zhang, Martin Morad
Rationale & methods
While signaling of cardiac SR by surface membrane proteins (ICa & INCX) is well studied, the regulation of mitochondrial Ca2+ by plasmalemmal proteins remains less explored. Here we have examined the signaling of mitochondria and SR by surface-membrane calcium-transporting proteins, using genetically engineered targeted fluorescent probes, mito-GCamP6 and R-CEPIA1er.
Results
In voltage-clamped and TIRF-imaged cardiomyocytes, low Na+ induced SR Ca2+ release was suppressed by short pre-exposures to ∼100 nM FCCP, suggesting mitochondrial Ca2+ contribution to low Na+ triggered SR Ca2+release. Even though low Na+- or caffeine-triggered SR Ca2+ release activated global mitochondrial Ca2+ uptake, focal mitochondrial Ca2+ signals varied in kinetics and magnitude, showing uptake or release of calcium, depending on cellular location of mitochondria. In spontaneously pacing cells, sustained caffeine exposures depleted the SR Ca2+ content activating mitochondrial Ca2+ uptake followed by sustained mitochondrial pacing. Spontaneous hiPSCCMs pacing was strongly suppressed by L-type calcium channels blockers, but not by inhibiting SERCA2a by CPA.
Conclusion
Spontaneous hiPSCCMs pacing is triggered by influx of calcium through L-type Ca2+ channel that gates the release of SR pools supplemented by NCX-mediated mitochondrial calcium contribution.
{"title":"Regulation of SR and mitochondrial Ca2+ signaling by L-type Ca2+ channels and Na/Ca exchanger in hiPSC–CMs","authors":"Xiao-Hua Zhang, Martin Morad","doi":"10.1016/j.ceca.2024.102985","DOIUrl":"10.1016/j.ceca.2024.102985","url":null,"abstract":"<div><h3>Rationale & methods</h3><div>While signaling of cardiac SR by surface membrane proteins (I<sub>Ca</sub> & I<sub>NCX</sub>) is well studied, the regulation of mitochondrial Ca<sup>2+</sup> by plasmalemmal proteins remains less explored. Here we have examined the signaling of mitochondria and SR by surface-membrane calcium-transporting proteins, using genetically engineered targeted fluorescent probes, mito-GCamP6 and R-CEPIA1er.</div></div><div><h3>Results</h3><div>In voltage-clamped and TIRF-imaged cardiomyocytes, low Na<sup>+</sup> induced SR Ca<sup>2+</sup> release was suppressed by short pre-exposures to ∼100 nM FCCP, suggesting mitochondrial Ca<sup>2+</sup> contribution to low Na<sup>+</sup> triggered SR Ca<sup>2+</sup>release. Even though low Na<sup>+</sup>- or caffeine-triggered SR Ca<sup>2+</sup> release activated <em><u>global</u></em> mitochondrial Ca<sup>2+</sup> uptake, <u>f</u><em><u>ocal</u></em> mitochondrial Ca<sup>2+</sup> signals varied in kinetics and magnitude, showing uptake or release of calcium, depending on cellular location of mitochondria. In spontaneously pacing cells, sustained caffeine exposures depleted the SR Ca<sup>2+</sup> content activating mitochondrial Ca<sup>2+</sup> uptake followed by sustained mitochondrial pacing. Spontaneous hiPSC<img>CMs pacing was strongly suppressed by L-type calcium channels blockers, but not by inhibiting SERCA2a by CPA.</div></div><div><h3>Conclusion</h3><div>Spontaneous hiPSC<img>CMs pacing is triggered by influx of calcium through L-type Ca<sup>2+</sup> channel that gates the release of SR pools supplemented by NCX-mediated mitochondrial calcium contribution.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"125 ","pages":"Article 102985"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.ceca.2024.102972
Ana M. Hernández-Vega , Refugio García-Villegas , Tamara Rosenbaum
The transient receptor potential vanilloid 4 (TRPV4) ion channel is a ubiquitously expressed Ca2+-permeable ion channel that controls intracellular calcium ([Ca2+]i) homeostasis in various types of cells. The physiological roles for TRPV4 are tissue specific and the mechanisms behind this specificity remain mostly unclarified. It is noteworthy that mutations in the TRPV4 channel have been associated to a broad spectrum of congenital diseases, with most of these mutations mainly resulting in gain-of-function. Mutations have been identified in human patients showing a variety of phenotypes and symptoms, mostly related to skeletal and neuromuscular disorders. Since TRPV4 is so widely expressed throughout the body, it comes as no surprise that the literature is growing in evidence linking this protein to malfunction in systems other than the skeletal and neuromuscular. In this review, we summarize the expression patterns of TRPV4 in several tissues and highlight findings of recent studies that address critical structural and functional features of this channel, particularly focusing on its interactions and signaling pathways related to Ca2+ entry. Moreover, we discuss the roles of TRPV4 mutations in some diseases and pinpoint some of the mechanisms underlying pathological states where TRPV4’s malfunction is prominent.
{"title":"Roles for TRPV4 in disease: A discussion of possible mechanisms","authors":"Ana M. Hernández-Vega , Refugio García-Villegas , Tamara Rosenbaum","doi":"10.1016/j.ceca.2024.102972","DOIUrl":"10.1016/j.ceca.2024.102972","url":null,"abstract":"<div><div>The transient receptor potential vanilloid 4 (TRPV4) ion channel is a ubiquitously expressed Ca<sup>2+</sup>-permeable ion channel that controls intracellular calcium ([Ca<sup>2+</sup>]<sub>i</sub>) homeostasis in various types of cells. The physiological roles for TRPV4 are tissue specific and the mechanisms behind this specificity remain mostly unclarified. It is noteworthy that mutations in the TRPV4 channel have been associated to a broad spectrum of congenital diseases, with most of these mutations mainly resulting in gain-of-function. Mutations have been identified in human patients showing a variety of phenotypes and symptoms, mostly related to skeletal and neuromuscular disorders. Since TRPV4 is so widely expressed throughout the body, it comes as no surprise that the literature is growing in evidence linking this protein to malfunction in systems other than the skeletal and neuromuscular. In this review, we summarize the expression patterns of TRPV4 in several tissues and highlight findings of recent studies that address critical structural and functional features of this channel, particularly focusing on its interactions and signaling pathways related to Ca<sup>2+</sup> entry. Moreover, we discuss the roles of TRPV4 mutations in some diseases and pinpoint some of the mechanisms underlying pathological states where TRPV4’s malfunction is prominent.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"124 ","pages":"Article 102972"},"PeriodicalIF":4.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-20DOI: 10.1016/j.ceca.2024.102970
Vikas Arige, David I. Yule
{"title":"PIP2 primes IP3 receptor activity: It takes at least three IP3s to open!","authors":"Vikas Arige, David I. Yule","doi":"10.1016/j.ceca.2024.102970","DOIUrl":"10.1016/j.ceca.2024.102970","url":null,"abstract":"","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"124 ","pages":"Article 102970"},"PeriodicalIF":4.3,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-17DOI: 10.1016/j.ceca.2024.102969
Qianru Mu , Jade L. Harris , David I. Yule , James T. Slama , Jonathan S. Marchant , Sandip Patel
{"title":"NAADP signaling: Master manipulation","authors":"Qianru Mu , Jade L. Harris , David I. Yule , James T. Slama , Jonathan S. Marchant , Sandip Patel","doi":"10.1016/j.ceca.2024.102969","DOIUrl":"10.1016/j.ceca.2024.102969","url":null,"abstract":"","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"124 ","pages":"Article 102969"},"PeriodicalIF":4.3,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-16DOI: 10.1016/j.ceca.2024.102971
Pablo Hernansanz-Agustín , Carmen Morales-Vidal , Enrique Calvo , Paolo Natale , Yolanda Martí-Mateos , Sara Natalia Jaroszewicz , José Luis Cabrera-Alarcón , Rebeca Acín-Pérez , Iván López-Montero , Jesús Vázquez , José Antonio Enríquez
In a comment to our recent publication, Nicholls question our results and interpretation based on theoretical arguments that reveal a profound misunderstanding of our publication.
{"title":"Electrogenic and non-electrogenic ion antiporters participate in controling membrane potential","authors":"Pablo Hernansanz-Agustín , Carmen Morales-Vidal , Enrique Calvo , Paolo Natale , Yolanda Martí-Mateos , Sara Natalia Jaroszewicz , José Luis Cabrera-Alarcón , Rebeca Acín-Pérez , Iván López-Montero , Jesús Vázquez , José Antonio Enríquez","doi":"10.1016/j.ceca.2024.102971","DOIUrl":"10.1016/j.ceca.2024.102971","url":null,"abstract":"<div><div>In a comment to our recent publication, Nicholls question our results and interpretation based on theoretical arguments that reveal a profound misunderstanding of our publication.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"124 ","pages":"Article 102971"},"PeriodicalIF":4.3,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-09DOI: 10.1016/j.ceca.2024.102968
Mohan Manjegowda, Bimal N. Desai
{"title":"Commentary on: Li et al.; Ca2+ transients on the T cell surface trigger rapid integrin activation in a timescale of seconds. Nature Communications (2024)","authors":"Mohan Manjegowda, Bimal N. Desai","doi":"10.1016/j.ceca.2024.102968","DOIUrl":"10.1016/j.ceca.2024.102968","url":null,"abstract":"","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"124 ","pages":"Article 102968"},"PeriodicalIF":4.3,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-02DOI: 10.1016/j.ceca.2024.102967
Sonja Sivcev , Stephanie Constantin , Kosara Smiljanic , Srdjan J. Sokanovic , Patrick A. Fletcher , Arthur S. Sherman , Hana Zemkova , Stanko S. Stojilkovic
The somatostatin (SST) receptor family controls pituitary hormone secretion, but the distribution and specific roles of these receptors on the excitability and voltage-gated calcium signaling of hormone producing pituitary cells have not been fully characterized. Here we show that the rat pituitary gland expressed Sstr1, Sstr2, Sstr3, and Sstr5 receptor genes in a cell type-specific manner: Sstr1 and Sstr2 in thyrotrophs, Sstr3 in gonadotrophs and lactotrophs, Sstr2, Sstr3, and Sstr5 in somatotrophs, and none in corticotrophs and melanotrophs. Most gonadotrophs and thyrotrophs spontaneously fired high-amplitude single action potentials, which were silenced by SST without affecting intracellular calcium concentrations. In contrast, lactotrophs and somatotrophs spontaneously fired low-amplitude plateau-bursting action potentials in conjunction with calcium transients, both of which were silenced by SST. Moreover, SST inhibited GPCR-induced voltage-gated calcium signaling and hormone secretion in all cell types expressing SST receptors, but the inhibition was more pronounced in somatotrophs. The pattern of inhibition of electrical activity and calcium signaling was consistent with both direct and indirect inhibition of voltage-gated calcium channels, the latter being driven by cell type-specific hyperpolarization. These results indicate that the action of SST in somatotrophs is enhanced by the expression of several types of SST receptors and their slow desensitization, that SST may play a role in the electrical resynchronization of gonadotrophs, thyrotrophs, and lactotrophs, and that the lack of SST receptors in corticotrophs and melanotrophs keeps them excitable and ready to responses to stress.
{"title":"Distribution and calcium signaling function of somatostatin receptor subtypes in rat pituitary","authors":"Sonja Sivcev , Stephanie Constantin , Kosara Smiljanic , Srdjan J. Sokanovic , Patrick A. Fletcher , Arthur S. Sherman , Hana Zemkova , Stanko S. Stojilkovic","doi":"10.1016/j.ceca.2024.102967","DOIUrl":"10.1016/j.ceca.2024.102967","url":null,"abstract":"<div><div>The somatostatin (SST) receptor family controls pituitary hormone secretion, but the distribution and specific roles of these receptors on the excitability and voltage-gated calcium signaling of hormone producing pituitary cells have not been fully characterized. Here we show that the rat pituitary gland expressed <em>Sstr1, Sstr2, Sstr3,</em> and <em>Sstr5</em> receptor genes in a cell type-specific manner: <em>Sstr1</em> and <em>Sstr2</em> in thyrotrophs, <em>Sstr3</em> in gonadotrophs and lactotrophs, <em>Sstr2, Sstr3</em>, and <em>Sstr5</em> in somatotrophs, and none in corticotrophs and melanotrophs. Most gonadotrophs and thyrotrophs spontaneously fired high-amplitude single action potentials, which were silenced by SST without affecting intracellular calcium concentrations. In contrast, lactotrophs and somatotrophs spontaneously fired low-amplitude plateau-bursting action potentials in conjunction with calcium transients, both of which were silenced by SST. Moreover, SST inhibited GPCR-induced voltage-gated calcium signaling and hormone secretion in all cell types expressing SST receptors, but the inhibition was more pronounced in somatotrophs. The pattern of inhibition of electrical activity and calcium signaling was consistent with both direct and indirect inhibition of voltage-gated calcium channels, the latter being driven by cell type-specific hyperpolarization. These results indicate that the action of SST in somatotrophs is enhanced by the expression of several types of SST receptors and their slow desensitization, that SST may play a role in the electrical resynchronization of gonadotrophs, thyrotrophs, and lactotrophs, and that the lack of SST receptors in corticotrophs and melanotrophs keeps them excitable and ready to responses to stress.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"124 ","pages":"Article 102967"},"PeriodicalIF":4.3,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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