Linked Life Data

15722340

Source:http://linkedlifedata.com/resource/pubmed/id/15722340

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2005-4-19
pubmed:abstractText
2-Aminoethyl diphenylborinate was recently identified as a chemical activator of TRPV1, TRPV2, and TRPV3, three heat-gated members of the transient receptor potential vanilloid (TRPV) ion channel subfamily. Here we demonstrated that two structurally related compounds, diphenylboronic anhydride (DPBA) and diphenyltetrahydrofuran (DPTHF), can also modulate the activity of these channels. DPBA acted as a TRPV3 agonist, whereas DPTHF exhibited prominent antagonistic activity. However, all three diphenyl-containing compounds promoted some degree of channel activation or potentiation, followed by channel block. Strong TRPV3 activation by DPBA often leads to the appearance of a secondary, enhanced, current phase. A similar biphasic response was observed during TRPV3 heat stimulation; an initial, gradually sensitizing phase (I(1)) was followed by an abrupt transition to a secondary phase (I(2)). I(2) was characterized by larger current amplitude, loss of outward rectification, and alterations in the following properties: permeability among cations; ruthenium red and DPTHF sensitivity; temperature dependence; and voltage-dependent gating. The I(1) to I(2) transition depended strongly on TRPV3 current density. Removal of extracellular divalent cations resulted in heat-evoked currents resembling I(2), whereas mutation of a putative Ca(2+)-binding residue in the pore loop domain, aspartate 641, facilitated detection of the I(1) to I(2) transition, suggesting that the conversion to I(2) resulted from the agonist- and time-dependent loss of divalent cationic inhibition. Primary keratinocytes overexpressing exogenous TRPV3 also exhibited biphasic agonist-evoked currents. Thus, strong activation by either chemical or thermal stimuli led to biphasic TRPV3 signaling behavior that may be associated with changes in the channel pore.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
15928-41
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Biphasic currents evoked by chemical or thermal activation of the heat-gated ion channel, TRPV3.
pubmed:affiliation
Departments of Biological Chemistry and Neuroscience, The Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't