Linked Life Data

12724311

Source:http://linkedlifedata.com/resource/pubmed/id/12724311

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
29
pubmed:dateCreated
2003-7-14
pubmed:abstractText
Most Ca2+-permeable ion channels are inhibited by increases in the intracellular Ca2+ concentration ([Ca2+]i), thus preventing potentially deleterious rises in [Ca2+]i. In this study, we demonstrate that currents through the osmo-, heat- and phorbol ester-sensitive, Ca2+-permeable nonselective cation channel TRPV4 are potentiated by intracellular Ca2+. Spontaneous TRPV4 currents and currents stimulated by hypotonic solutions or phorbol esters were reduced strongly at all potentials in the absence of extracellular Ca2+. The other permeant divalent cations Ba2+ and Sr2+ were less effective than Ca2+ in supporting channel activity. An intracellular site of Ca2+ action was supported by the parallel decrease in spontaneous currents and [Ca2+]i on removal of extracellular Ca2+ and the ability of Ca2+ release from intracellular stores to restore TRPV4 activity in the absence of extracellular Ca2+. During TRPV4 activation by hypotonic solutions or phorbol esters, Ca2+ entry through the channel increased the rate and extent of channel activation. Currents were also potentiated by ionomycin in the presence of extracellular Ca2+. Ca2+-dependent potentiation of TRPV4 was often followed by inhibition. By mutagenesis, we localized the structural determinant of Ca2+-dependent potentiation to an intracellular, C-terminal calmodulin binding domain. This domain binds calmodulin in a Ca2+-dependent manner. TRPV4 mutants that did not bind calmodulin lacked Ca2+-dependent potentiation. We conclude that TRPV4 activity is tightly controlled by intracellular Ca2+. Ca2+ entry increases both the rate and extent of channel activation by a calmodulin-dependent mechanism. Excessive increases in [Ca2+]i via TRPV4 are prevented by a Ca2+-dependent negative feedback mechanism.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
26541-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12724311-Amino Acid Sequence, pubmed-meshheading:12724311-Amino Acid Substitution, pubmed-meshheading:12724311-Base Sequence, pubmed-meshheading:12724311-Binding Sites, pubmed-meshheading:12724311-Calcium, pubmed-meshheading:12724311-Calmodulin, pubmed-meshheading:12724311-Cation Transport Proteins, pubmed-meshheading:12724311-Cations, Divalent, pubmed-meshheading:12724311-Cell Line, pubmed-meshheading:12724311-Cloning, Molecular, pubmed-meshheading:12724311-DNA, pubmed-meshheading:12724311-Feedback, pubmed-meshheading:12724311-Humans, pubmed-meshheading:12724311-Ion Channels, pubmed-meshheading:12724311-Ionomycin, pubmed-meshheading:12724311-Ionophores, pubmed-meshheading:12724311-Kinetics, pubmed-meshheading:12724311-Molecular Sequence Data, pubmed-meshheading:12724311-Mutagenesis, Site-Directed, pubmed-meshheading:12724311-Protein Binding, pubmed-meshheading:12724311-Recombinant Proteins, pubmed-meshheading:12724311-TRPV Cation Channels
pubmed:year
2003
pubmed:articleTitle
Ca2+-dependent potentiation of the nonselective cation channel TRPV4 is mediated by a C-terminal calmodulin binding site.
pubmed:affiliation
Institut für Pharmakologie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Thielallee 67-73, 14195 Berlin, Germany.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't