Linked Life Data

19852931

Source:http://linkedlifedata.com/resource/pubmed/id/19852931

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-11-25
pubmed:abstractText
Large conductance, calcium- and voltage-gated potassium (BK) channels regulate numerous physiological processes. While most basic functional characteristics of native BK channels are reproduced by BK alpha (slo1) subunit homotetramers, key biophysical and pharmacological properties are drastically modified by the presence of auxiliary beta subunits (encoded by KCNMB1-4). Numerous physiological steroids, including sex hormones, gluco- and mineralocorticoids, activate beta subunit-containing BK channels, yet these steroids appear to be sensed by different types of beta subunits, with some steroids being sensed by homomeric slo1 channels as well. We recently showed that beta1 sensitizes the BK channel to microM concentrations of lithocholate (LC). Following expression of rat cerebral artery myocyte slo1 subunits ("cbv1") with beta1, beta2, beta3 or beta4 in Xenopus laevis oocytes we now demonstrate that BK beta2, beta3 and beta4 subunits fail to substitute for beta1 in providing LC-sensitivity (150 microM) to the BK channel. These findings document for the first time a rather selective steroid activation of BK channels via a particular channel accessory subunit. In addition, LC routinely activated native BK channels in myocytes freshly isolated from rat cerebral artery smooth muscle, where BK beta1 is highly expressed, while failing to do so in skeletal (flexor digitorum brevis) muscle, where BK beta1 expression is negligible. This indicates that the native environment of the BK channel sustains the LC-sensitivity distinctly provided to the BK channel by beta1 subunits. Our study indicates that LC represents a unique tool to probe the presence of functional beta1-subunits and selectively activate BK channels in tissues that highly express KCNMB1.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1090-2104
pubmed:author
pubmed:issnType
Electronic
pubmed:day
18
pubmed:volume
390
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
995-1000
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Channel beta2-4 subunits fail to substitute for beta1 in sensitizing BK channels to lithocholate.
pubmed:affiliation
Department of Pharmacology, University of Tennessee HSC, 874 Union Ave, Memphis, TN 38163, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural