Linked Life Data

17125805

Source:http://linkedlifedata.com/resource/pubmed/id/17125805

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-2-16
pubmed:abstractText
Roscovitine potently inhibits cyclin-dependent kinases (CDK) and can independently slow the closing of neuronal (CaV2.2) calcium channels. We were interested if this drug could affect other ion channels similarly. Using whole cell recordings, we found that roscovitine specifically slows deactivation of all CaV2 channels (N, P/Q and R) by binding to the open state. This effect had a rapid onset and EC(50)=54, 120 and 54microM for N-, P/Q-, and R-type channels, respectively. Deactivation of other channel types was not slowed, including L-type calcium channels (CaV1.2, CaV1.3), potassium channels (native, Kv4.2, Kv2.1 and Kv1.3), and native sodium channels. However, most of the channels tested were inhibited by roscovitine. The inhibition was characterized by slow development and a lower affinity (EC(50)=100-300microM). Surprisingly, potassium channels were rapidly inhibited with an EC(50)=23microM, which is similar to the EC(50) for roscovitine block of cell division [Meijer, L., Borgne, A., Mulner, O., Chong, J., Blow, J., Inagaki, N., Inagaki, M., Delcros, J., Moulinoux, J., 1997. Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5. Eur. J. Biochem. 243, 527-536]. Potassium current inhibition seemed to result from open channel block. The high potency of these two rapid onset effects makes them complicating factors for ongoing clinical trials and research using roscovitine. Thus, the physiology and pharmacology of slow CaV2 deactivation and potassium channel block must be explored.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0028-3908
pubmed:author
pubmed:issnType
Print
pubmed:volume
52
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
883-94
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Roscovitine differentially affects CaV2 and Kv channels by binding to the open state.
pubmed:affiliation
Department of Physiology, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
pubmed:publicationType
Journal Article