| Voltage-dependent Ba2+ permeation through store-operated CRAC channels: implications for channel selectivity. | |
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MedLine Citation:
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PMID: 17343911 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Store-operated Ca2+ entry through CRAC channels is a major route for Ca2+ influx in non-excitable cells. Studies on store-operated channel selectivity using fluorescent dyes have found that the channels are impermeable to Ba2+. Furthermore, in such studies, agonists have been reported to increase Ba2+ influx, leading to the conclusion that additional Ca2+ entry pathways (permeable to Ba2+) co-exist with the Ba2+-impermeable store-operated channels. However, patch clamp experiments demonstrate that CRAC channels are permeable to Ba2+. We have addressed this paradox using fluorescence measurements and whole cell patch clamp recordings of ICRAC. In store-depleted cells loaded with fura 2, Ba2+ application results in a slower and smaller rise in fluorescence than is the case with Ca2+. Ba2+, unlike Ca2+, depolarises the membrane potential by approximately 40 mV, due to rapid block of an inwardly rectifying K+ current. Although Ba2+ permeates CRAC channels at very negative potentials in patch clamp recordings, Ba2+ permeation is steeply voltage-dependent. This combination of Ba2+-dependent depolarisation and voltage-dependent Ba2+ permeation accounts for the apparent lack of Ba2+ permeation through store-operated channels seen in fluorescence experiments. Our findings identify major limitations with the use of Ba2+ as a surrogate for Ca2+ in probing Ca2+ entry pathways and raise the possibility that some of the previous reports proposing multiple Ca2+ entry pathways based on Ba2+ entry into fura 2-loaded cells could be explained by voltage-dependent Ba2+ permeation through CRAC channels. |
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Authors:
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Daniel Bakowski; Anant B Parekh |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-03-06 |
Journal Detail:
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Title: Cell calcium Volume: 42 ISSN: 0143-4160 ISO Abbreviation: Cell Calcium Publication Date: 2007 Sep |
Date Detail:
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Created Date: 2007-07-25 Completed Date: 2008-01-22 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8006226 Medline TA: Cell Calcium Country: Scotland |
Other Details:
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Languages: eng Pagination: 333-9 Citation Subset: IM |
Affiliation:
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Department of Physiology, University of Oxford, Parks Road, Oxford OX1 3PT, UK. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Barium / metabolism* Calcium / metabolism* Calcium Channels / metabolism* Cell Line Fluorescent Dyes / metabolism Fura-2 Ion Channel Gating Membrane Potentials / physiology Patch-Clamp Techniques Potassium Channels / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Calcium Channels; 0/Fluorescent Dyes; 0/Potassium Channels; 7440-39-3/Barium; 7440-70-2/Calcium; 96314-98-6/Fura-2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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