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Requirement of subunit expression for cAMP-mediated regulation of a heart potassium channel.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America . 2/18/2003, Vol. 100 Issue 4, p2122. 6p. 8 Black and White Photographs, 2 Diagrams, 16 Graphs. - Publication Year :
- 2003
-
Abstract
- β-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[sub Ks]). Mutations in either KCNQ1 or KCNE1, the l[sub 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 cAMPdependent 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *BETA adrenoceptors
*HEART beat
*GENETIC mutation
*POTASSIUM channels
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 100
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 9259256
- Full Text :
- https://doi.org/10.1073/pnas.0434935100