Linked Life Data

19783046

Source:http://linkedlifedata.com/resource/pubmed/id/19783046

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-10-19
pubmed:abstractText
We investigated the biophysical mechanism of inhibition of recombinant T-type calcium channels Ca(V)3.1 and Ca(V)3.2 by nitrous oxide (N(2)O). To identify functionally important channel structures, chimeras with reciprocal exchange of the N-terminal domains I and II and C-terminal domains III and IV were examined. In whole-cell recordings N(2)O significantly inhibited Ca(V)3.2, and - less pronounced - Ca(V)3.1. A Ca(V)3.2-prevalent inhibition of peak currents was also detected in cell-attached multi-channel patches. In cell-attached patches containing < or = 3 channels N(2)O reduced average peak current of Ca(V)3.2 by decreasing open probability and open time duration. Effects on Ca(V)3.1 were smaller and mediated by a reduced fraction of sweeps containing channel activity. Without drug, single Ca(V)3.1 channels were significantly less active than Ca(V)3.2. Chimeras revealed that domains III and IV control basal gating properties. Domains I and II, in particular a histidine residue within Ca(V)3.2 (H191), are responsible for the subtype-prevalent N(2)O inhibition. Our study demonstrates the biophysical (open times, open probability) and structural (domains I and II) basis of action of N(2)O on Ca(V)3.2. Such a fingerprint of single channels can help identifying the molecular nature of native channels. This is exemplified by a characterization of single channels expressed in human hMTC cells as functional homologues of recombinant Ca(V)3.1.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1532-1991
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
293-302
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Structural and biophysical determinants of single Ca(V)3.1 and Ca(V)3.2 T-type calcium channel inhibition by N(2)O.
pubmed:affiliation
Department of Pharmacology, University of Cologne, 50931 Koeln, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't