Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2001-5-30
pubmed:abstractText
The mechanism for coupling between Ca(2+) stores and store-operated channels (SOCs) is an important but unresolved question. Although SOCs have not been molecularly identified, transient receptor potential (TRP) channels share a number of operational parameters with SOCs. The question of whether activation of SOCs and TRP channels is mediated by the inositol 1,4,5-trisphosphate receptor (InsP(3)R) was examined using the permeant InsP(3)R antagonist, 2-aminoethoxydiphenyl borate (2-APB) in both mammalian and invertebrate systems. In HEK293 cells stably transfected with human TRPC3 channels, the actions of 2-APB to block carbachol-induced InsP(3)R-mediated store release and carbachol-induced Sr(2+) entry through TRPC3 channels were both reversed at high agonist levels, suggesting InsP(3)Rs mediate TRPC3 activation. However, electroretinogram recordings of the light-induced current in Drosophila revealed that the TRP channel-mediated responses in wild-type as well as trp and trpl mutant flies were all inhibited by 2-APB. This action of 2-APB is likely InsP(3)R-independent since InsP(3)Rs are dispensable for the light response. We used triple InsP(3)R knockout DT40 chicken B-cells to further assess the role of InsP(3)Rs in SOC activation. (45)Ca(2+) flux analysis revealed that although DT40 wild-type cells retained normal InsP(3)Rs mediating 2-APB-sensitive Ca(2+) release, the DT40InsP(3)R-k/o cells were devoid of functional InsP(3)Rs. Using intact cells, all parameters of Ca(2+) store function and SOC activation were identical in DT40wt and DT40InsP(3)R-k/o cells. Moreover, in both cell lines SOC activation was completely blocked by 2-APB, and the kinetics of action of 2-APB on SOCs (time dependence and IC(50)) were identical. The results indicate that (a) the action of 2-APB on Ca(2+) entry is not mediated by the InsP(3)R and (b) the effects of 2-APB provide evidence for an important similarity in the function of invertebrate TRP channels, mammalian TRP channels, and mammalian store-operated channels.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/2-aminoethoxydiphenyl borate, http://linkedlifedata.com/resource/pubmed/chemical/Adenosine, http://linkedlifedata.com/resource/pubmed/chemical/Boron Compounds, http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channel Agonists, http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels, http://linkedlifedata.com/resource/pubmed/chemical/Carbachol, http://linkedlifedata.com/resource/pubmed/chemical/ITPR1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Inositol 1,4,5-Trisphosphate..., http://linkedlifedata.com/resource/pubmed/chemical/Muscarinic Antagonists, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear, http://linkedlifedata.com/resource/pubmed/chemical/Strontium, http://linkedlifedata.com/resource/pubmed/chemical/adenophostin A
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
18888-96
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11259416-Adenosine, pubmed-meshheading:11259416-Animals, pubmed-meshheading:11259416-Animals, Genetically Modified, pubmed-meshheading:11259416-Boron Compounds, pubmed-meshheading:11259416-Calcium, pubmed-meshheading:11259416-Calcium Channel Agonists, pubmed-meshheading:11259416-Calcium Channels, pubmed-meshheading:11259416-Carbachol, pubmed-meshheading:11259416-Cell Line, pubmed-meshheading:11259416-Chickens, pubmed-meshheading:11259416-Dose-Response Relationship, Drug, pubmed-meshheading:11259416-Drosophila, pubmed-meshheading:11259416-Electroretinography, pubmed-meshheading:11259416-Humans, pubmed-meshheading:11259416-Inositol 1,4,5-Trisphosphate Receptors, pubmed-meshheading:11259416-Light, pubmed-meshheading:11259416-Muscarinic Antagonists, pubmed-meshheading:11259416-Mutation, pubmed-meshheading:11259416-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:11259416-Strontium, pubmed-meshheading:11259416-Time Factors, pubmed-meshheading:11259416-Transfection
pubmed:year
2001
pubmed:articleTitle
Assessment of the role of the inositol 1,4,5-trisphosphate receptor in the activation of transient receptor potential channels and store-operated Ca2+ entry channels.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't