Linked Life Data

17068294

Source:http://linkedlifedata.com/resource/pubmed/id/17068294

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2006-11-23
pubmed:abstractText
Cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH) has devastating consequences. Oxyhemoglobin (oxyhb) has been implicated in SAH-induced cerebral vasospasm as it causes cerebral artery constriction and increases tyrosine kinase activity. Voltage-dependent, Ca(2+)-selective and K(+)-selective ion channels play an important role in the regulation of cerebral artery diameter and represent potential targets of oxyhb. Here we provide novel evidence that oxyhb selectively decreases 4-aminopyridine sensitive, voltage-dependent K(+) channel (K(v)) currents by approximately 30% in myocytes isolated from rabbit cerebral arteries but did not directly alter the activity of voltage-dependent Ca(2+) channels or large conductance Ca(2+)-activated (BK) channels. A combination of tyrosine kinase inhibitors (tyrphostin AG1478, tyrphostin A23, tyrphostin A25, genistein) abolished both oxyhb-induced suppression of K(v) channel currents and oxyhb-induced constriction of isolated cerebral arteries. The K(v) channel blocker 4-aminopyridine also inhibited oxyhb-induced cerebral artery constriction. The observed oxyhb-induced decrease in K(v) channel activity could represent either channel block, or a decrease in K(v) channel density on the plasma membrane. To explore whether oxyhb altered trafficking of K(v) channels to the plasma membrane, we used an antibody generated against an extracellular epitope of K(v)1.5 channels. In the presence of oxyhb, staining of K(v)1.5 on the plasma membrane surface was markedly reduced. Furthermore, oxyhb caused a loss of spatial distinction between staining with K(v)1.5 and the general anti-phosphotyrosine antibody PY-102. We propose that oxyhb-induced suppression of K(v) currents occurs via a mechanism involving enhanced tyrosine kinase activity and channel endocytosis. This novel mechanism may contribute to oxyhb-induced cerebral artery constriction following SAH.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
24
pubmed:volume
99
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1252-60
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17068294-4-Aminopyridine, pubmed-meshheading:17068294-Animals, pubmed-meshheading:17068294-Cell Membrane, pubmed-meshheading:17068294-Cerebral Arteries, pubmed-meshheading:17068294-Electric Conductivity, pubmed-meshheading:17068294-Enzyme Inhibitors, pubmed-meshheading:17068294-Fluorescent Antibody Technique, pubmed-meshheading:17068294-Humans, pubmed-meshheading:17068294-Kv1.5 Potassium Channel, pubmed-meshheading:17068294-Large-Conductance Calcium-Activated Potassium Channels, pubmed-meshheading:17068294-Male, pubmed-meshheading:17068294-Muscle Cells, pubmed-meshheading:17068294-Oxyhemoglobins, pubmed-meshheading:17068294-Potassium Channel Blockers, pubmed-meshheading:17068294-Potassium Channels, Voltage-Gated, pubmed-meshheading:17068294-Protein-Tyrosine Kinases, pubmed-meshheading:17068294-Rabbits, pubmed-meshheading:17068294-Staining and Labeling, pubmed-meshheading:17068294-Subarachnoid Hemorrhage, pubmed-meshheading:17068294-Vasoconstriction
pubmed:year
2006
pubmed:articleTitle
Oxyhemoglobin-induced suppression of voltage-dependent K+ channels in cerebral arteries by enhanced tyrosine kinase activity.
pubmed:affiliation
Department of Pharmacology, Division of Neurological Surgery, University of Vermont College of Medicine, Burlington 05405-0068, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural