User Visitor Login
/images/graph_sv_i.gif
English only
EPFL > FSV > BBP > Channelpedia
Ion channels
References
Reports
SEARCH IN WIKI
Logged in as a Visitor.

Requirement of subunit expression for cAMP-mediated regulation of a heart potassium channel.

Junko Kurokawa, Lei Chen, Robert S Kass

Proc. Natl. Acad. Sci. U.S.A., 2003 Feb 18 , 100, 2122-7

Beta-adrenergic receptor stimulation increases heart rate and shortens ventricular action-potential duration, the latter effect due in part to a cAMP-dependent increase in the slow outward potassium current (I(Ks)). Mutations in either KCNQ1 or KCNE1, the I(Ks) subunits, are associated with variants (LQT-1 and LQT-5) of the congenital long QT syndrome. We now show that cAMP-mediated functional regulation of KCNQ1/KCNE1 channels, a consequence of cAMP-dependent protein kinase A phosphorylation of the KCNQ1 N terminus, requires coexpression of KCNQ1 with KCNE1, its auxiliary subunit. Further, at least two KCNE1 mutations linked to LQT-5 (D76N and W87R) cause functional disruption of cAMP-mediated KCNQ1/KCNE1-channel regulation despite the response of the substrate protein (KCNQ1) to protein kinase A phosphorylation. Transduction of protein phosphorylation into physiologically necessary channel function represents a previously uncharacterized role for the KCNE1 auxiliary subunit, which can be disrupted in LQT-5.

http://www.ncbi.nlm.nih.gov/pubmed/12566567