2024-03-28T18:06:21Zhttp://uvadoc.uva.es/oai/requestoai:uvadoc.uva.es:10324/250242021-05-21T21:05:00Zcom_10324_32522com_10324_952com_10324_894com_10324_43677com_10324_954com_10324_1134com_10324_931col_10324_32525col_10324_43680col_10324_1215
Calcium signalling in cardiac muscle cells
Withrow, Gil Wier
López López, José Ramón
Shacklock, Philip S.
Balke, C. William
In heart cells, severa! distinct kinds of transient spatial patterns of cytoplasmic calcium ion concentration ([ Ca2 + )¡) can be observed: (1) [ Ca2 + )¡ waves, in which regions of spontaneously increased [ Ca2 + ] ; propagate at high velocity (100 ¡.im/s) through the cell; (2) Ca2 + 'sparks', which are spontaneous, non-propagating changes in [ Ca2 + ] ; that are localized in small ( == 2 ¡.im) subcellular regions; and (3) evoked [ Ca2 + )¡ transients that are elicited by electrical depolarization, in association with normal excitation-contraction (E
C) coupling. In confocal [ Ca2 + ] ¡ images, evoked [ Ca2 + ] ; transients appear to be nearly spatially uniform throughout the cell, except during their rising phase or during small depolarizations. In contrast to [Ca2 + )¡ waves and spontaneous Ca2 + sparks, evoked [ Ca2 + ] ; transients are triggered by L-type Ca2 + channel current and they are 'controlled', in the sense that stopping the L-type Ca2 + current stops them. Despite their different characteristics, ali three types of Ca2 + transient involve Ca2 + -induced release of Ca2 + from the sarcoplasmic reticulum. Here, we address the question of how the autocatalytic process of Ca2 + -induced Ca2 + release, which can easily be understood to underlie spontaneous regenerative ('uncontrolled'), propagating [Ca2 + )¡ waves, might be 'harnessed', under other circumstances, to produce controlled changes in [ Ca2 + ]¡, as during normal excitation-contraction coupling, or changes in [ Ca2 + )¡ that do not propagate. We discuss our observations of Ca2 + waves, Ca2 + sparks and normal Ca2 + transients in heart cells and review our results on the 'gain' of Ca2 + -induced Ca2 + release. We discuss a model involving Ca2 + microdomains beneath L-type Ca2 + channels, and clusters of Ca2 + -activated Ca2 + release channels in the sarcoplasmic reticulum which may form the basis of the answer to this question
2017-08-24T07:53:41Z
2017-08-24T07:53:41Z
2017-08-24T07:53:41Z
1995
info:eu-repo/semantics/conferenceObject
Calcium waves, gradients and oscillations. Ciba Foundation Symposium 188. Chichester: Willey, 1995, p.146-164
http://uvadoc.uva.es/handle/10324/25024
eng
https://onlinelibrary.wiley.com/doi/10.1002/9780470514696.ch9
info:eu-repo/semantics/openAccess
University of Maryland. School of Medicine
oai:uvadoc.uva.es:10324/660462024-02-08T20:00:59Zcom_10324_1134com_10324_931com_10324_894col_10324_1215
Channel complexes involved in remodeling of store-operated channels in colon cancer cells and their reversal by DFMO
González Gutiérrez, Lucía
Store-operated Ca2+ entry (SOCE) is the most important Ca2+ entry pathway in non-excitable cells. Colorectal cancer (CRC) show decreased Ca2+ store content and enhanced SOCE that are associated to remodeling of store-operated channels (SOCs), in addition its correlate with cancer hallmarks. Ca2+ remodeling in CRC may consist of changes in expression of Ca2+ channels and pumps and are associated to interaction among different molecular players: nonselective currents driven by Orai1, Orai3 and TRPC1 channels and Stim1 and Stim2 sensors. Difluoromethylornithine (DFMO), a suicide inhibitor of ornithine decarboxylase (ODC), is a strongly preventor of CRC. We asked whether polyamine depletion could be reverse Ca2+ remodelling interactions in CRC. We found that the principal players in normal mucosa cells in SOCE are Orai1 and Stim2, TRPC1 and Stim1 also are presented in low levels. It seems that all this molecules make week interactions between them. However, store-operated channels in CRC display enhanced dual interactions between TRPC1, Stim1 and Orai1 compared to normal cells. Moreover, DFMO treatment decreases specifically the interaction between TRPC1 and Stim1. These data are consistent with previous results that looked like DFMO treatment in CRC cells, specifically affecting the suppression of TRPC1 and Stim1. These results suggest that polyamines contribute to Ca2+ channel remodelling interactions in CRC and DFMO may prevent CRC by reversing channel remodeling.
2024-02-08T17:52:15Z
2024-02-08T17:52:15Z
2024-02-08T17:52:15Z
2020
info:eu-repo/semantics/conferenceObject
Miembros del comité organizador del jECS fueron Dr. Roy Tadayon Dr Malene Brohus. El título es 1 st Junior European Calcium Society Virtual Meeting, se celebró los días 20 y 21 de octubre de 2020 online pero la entidad de organización fue la Universidad dCalótlica de Lovaina (Bélgica).
https://uvadoc.uva.es/handle/10324/66046
10.1016/j.bbamcr.2021.118999
spa
https://www.sciencedirect.com/science/article/pii/S0167488921000537
info:eu-repo/semantics/openAccess
Instituto de Biología y Genética Molecular (UVa-CSIC) / Universidad de Extremadura / Elsevier
oai:uvadoc.uva.es:10324/661542024-02-12T20:00:40Zcom_10324_1134com_10324_931com_10324_894col_10324_1215
Inhibition of polyamine biosynthesis by DFMO reverts partially Ca2+ remodeling in colon cancer cells
González Gutiérrez, Lucía
Recently we have shown that colon cancer cells undergo remodeling of intracellular Ca2+ homeostasis including changes in store-operated Ca2+ entry (SOCE), store-operated currents and Ca2+ store content associated to changes in molecular players involved in SOCE (Sobradillo et al., 2014). Reversing this remodeling could contribute to protection against cancer and cancer chemoprevention. Difluoromethylornithine (DFMO) or Eflornithine is a suicide inhibitor of ornithine decarboxylase (ODC), the limiting step in the synthesis of polyamines that is considered one of the best chemopreventive compounds against colon cancer. Here we tested the effects of DFMO treatment on SOCE, SOCs, Ca2+ store content, the molecular players involved and resistance to cell death, a critical cancer hallmark. We found that ODC was largely overexpressed in colon cancer cells suggesting increased synthesis of polyamines in colon cancer cells. Short-term treatment with DFMO (500 µM, 12 h) decreased significantly SOCE and store-operated currents in colon cancer cells. DFMO had no effect on Icrac but prevented selectively the appearance of the outward component of store-operated current likely mediated by TRPC1. DFMO also increased Ca2+ store content and the fraction of cells undergoing early apoptosis induced by H2O2. At the molecular level, we found DFMO tend to decrease all molecular players involved in SOCE except Stim2 but the effects were statistically significant only for TRPC1 mRNA. In summary, inhibition of polyamine synthesis decreases SOCE and SOCs in human colon cancer cells acting probably on expression of TRPC1 and tends to increase Ca2+ store content and susceptibility to apoptosis in human colon cancer cells. Thus, reverting partially Ca2+ remodeling in colon cancer cells and likely contributing to colon cancer chemoprevention.
2024-02-12T10:34:12Z
2024-02-12T10:34:12Z
2024-02-12T10:34:12Z
2016-11
info:eu-repo/semantics/conferenceObject
Comité organizador ConBioPreVal, 2016, Universidad de Valencia. III Conbiopreval, I Congreso Nacional Biomedicina Jóvenes Investigadores. Valencia, Centro de Investigación Príncipe Pelipe 2016.
https://uvadoc.uva.es/handle/10324/66154
eng
info:eu-repo/semantics/openAccess
Instituto de Biología y Genética Molecular (UVa-CSIC)
oai:uvadoc.uva.es:10324/661592024-02-12T20:00:40Zcom_10324_1134com_10324_931com_10324_894col_10324_1215
Effects of a cancer chemopreventive compound on calcium channel remodeling in colon carcinoma cells
González Gutiérrez, Lucía
Calcio
Store-operated Ca2+ entry (SOCE) is the most important Ca2+ entry pathway in non-excitable cells. Colorectal cancer (CRC) show decreased Ca2+ store content and enhanced SOCE that correlate with cancer hallmarks and are associated to remodeling of store-operated channels (SOCs). Normal colonic cells display small, Ca2+-selective currents driven by Orai1 channels. In contrast, CRC cells display larger, non-selective currents driven by Orai1 and TRPC1 channels. Difluoromethylornithine (DFMO), a suicide inhibitor of ornithine decarboxylase (ODC), the limiting step in polyamine biosynthesis, strongly prevents CRC, particularly when combined with sulindac. We asked whether DFMO may reverse SOC remodeling in CRC. We found that CRC cells overexpress ODC and treatment with DFMO decreases cancer hallmarks including enhanced cell proliferation and apoptosis resistance. Consistently, DFMO enhances Ca2+ store content and decreases SOCE in CRC cells. Moreover, DFMO abolish selectively the TRPC1-dependent component of SOCs characteristic of CRC cells and this effect is reversed by the polyamine putrescine. Combination of DFMO and sulindac inhibit both SOC components and abolish SOCE in CRC cells. Finally, DFMO treatment inhibits expression of TRPC1 and STIM1 in CRC cells. These results suggest that polyamines contribute to Ca2+ channel remodeling in CRC and DFMO may prevent CRC by reversing channel remodeling.
2024-02-12T11:00:16Z
2024-02-12T11:00:16Z
2024-02-12T11:00:16Z
2015
info:eu-repo/semantics/conferenceObject
Coordinador Rubén Vicente; Universidad de Pompeu Fabra. V Congreso Red Española de Canales Iónicos (RECI). Barcelona 2015.
https://uvadoc.uva.es/handle/10324/66159
eng
info:eu-repo/semantics/openAccess
Instituto de Biología y Genética Molecular (UVa-CSIC)