Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
48
pubmed:dateCreated
1997-1-7
pubmed:abstractText
Phenylalanine 1489 in the inactivation gate of the rat brain IIA sodium channel alpha subunit is required for stable inactivation. It is proposed to move into the intracellular mouth of the pore and occlude it during inactivation, but direct evidence for movement of this residue during inactivation has not been presented. We used the substituted cysteine accessibility method to test the availability of a cysteine residue substituted at position 1489 to modification by methanethiosulfonate reagents applied from the cytoplasmic side. Mutation of Phe-1489 to Cys results in a small (8%) fraction of noninactivating current. Ag+ and methanethiosulfonate reagents irreversibly slowed the inactivation rate and increased the fraction of noninactivating current of F1489C but not wild-type channels. Single channel analysis showed that modification slowed inactivation from both closed and open states and destabilized the inactivated state. Depolarization prevented rapid modification of Cys-1489 by these reagents, and the voltage dependence of their reaction rate correlated closely with steady-state inactivation. Modification was not detectably voltage-dependent at voltages more negative than channel gating. Our results show that, upon inactivation, Phe-1489 in the inactivation gate moves from an exposed and modifiable position outside the membrane electric field to a buried and inaccessible position, perhaps in or near the intracellular mouth of the channel pore.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
29
pubmed:volume
271
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
30971-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Movement of the Na+ channel inactivation gate during inactivation.
pubmed:affiliation
Department of Pharmacology, University of Washington, Seattle, Washington 98195-7280, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't