期刊
CELL CALCIUM
卷 54, 期 5, 页码 362-374出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.ceca.2013.08.005
关键词
TRPV1; TRPV4; TRPM3; TRPM8; TRPA1; PMCA; Calcium imaging; Fluorescence-activated cell sorting
类别
资金
- Belgian Federal Government [IUAP P7/13]
- Research Foundation-Flanders [G.0565.07, G.0686.09, G.A022.11N]
- Research Council of the KU Leuven [GOA 2009/07, EF/95/010, PFV/10/006]
It is often observed in intracellular Ca2+ imaging experiments that the amplitudes of the Ca2+ signals elicited by newly characterized TRP agonists do not correlate with the amplitudes of the responses evoked subsequently by a specific potent agonist. We investigated this rather controversial phenomenon by first testing whether it is inherent to the comparison of the effects of weak and strong stimuli. Using five well-characterized TRP channel agonists in commonly used heterologous expression systems we found that the correlation between the amplitudes of the Ca2+ signals triggered by two sequentially applied stimuli is only high when both stimuli are strong. Using mathematical simulations of intracellular Ca2+ dynamics we illustrate that the innate heterogeneity in expression and functional properties of Ca2+ extrusion (e.g. plasma membrane Ca2+ ATPase) and influx (TRP channels) pathways across a cellular population is a sufficient condition for low correlation between the amplitude of Ca2+ signals elicited by weak and strong stimuli. Taken together, our data demonstrate that this phenomenon is an expected outcome of intracellular Ca2+ imaging experiments that cannot be taken as evidence for lack of specificity of low-efficacy stimuli, or as an indicator of the need of other cellular components for channel stimulation. (C) 2013 Elsevier Ltd. All rights reserved.
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