| Cardiac small conductance Ca2+-activated K+ channel subunits form heteromultimers via the coiled-coil domains in the C termini of the channels. | |
| | |
MedLine Citation:
|
PMID: 20689065 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
RATIONALE: Ca(2+)-activated K(+) channels are present in a wide variety of cells. We have previously reported the presence of small conductance Ca(2+)-activated K(+) (SK or K(Ca)) channels in human and mouse cardiac myocytes that contribute functionally toward the shape and duration of cardiac action potentials. Three isoforms of SK channel subunits (SK1, SK2, and SK3) are found to be expressed. Moreover, there is differential expression with more abundant SK channels in the atria and pacemaking tissues compared with the ventricles. SK channels are proposed to be assembled as tetramers similar to other K(+) channels, but the molecular determinants driving their subunit interaction and assembly are not defined in cardiac tissues. OBJECTIVE: To investigate the heteromultimeric formation and the domain necessary for the assembly of 3 SK channel subunits (SK1, SK2, and SK3) into complexes in human and mouse hearts. METHODS AND RESULTS: Here, we provide evidence to support the formation of heteromultimeric complexes among different SK channel subunits in native cardiac tissues. SK1, SK2, and SK3 subunits contain coiled-coil domains (CCDs) in the C termini. In vitro interaction assay supports the direct interaction between CCDs of the channel subunits. Moreover, specific inhibitory peptides derived from CCDs block the Ca(2+)-activated K(+) current in atrial myocytes, which is important for cardiac repolarization. CONCLUSIONS: The data provide evidence for the formation of heteromultimeric complexes among different SK channel subunits in atrial myocytes. Because SK channels are predominantly expressed in atrial myocytes, specific ligands of the different isoforms of SK channel subunits may offer a unique therapeutic opportunity to directly modify atrial cells without interfering with ventricular myocytes. |
| | |
Authors:
|
Dipika Tuteja; Sassan Rafizadeh; Valeriy Timofeyev; Shuyun Wang; Zheng Zhang; Ning Li; Robertino K Mateo; Anil Singapuri; J Nilas Young; Anne A Knowlton; Nipavan Chiamvimonvat |
Related Documents
:
|
19917615 - The beta subunit of voltage-gated ca2+ channels interacts with and regulates the activi... 12355225 - Cloned bullfrog skin sodium (fenac) and xenac subunits hybridize to form functional sod... 8107965 - A beta-subunit normalizes the electrophysiological properties of a cloned n-type ca2+ c... 17686775 - Plasma membrane targeting is essential for rem-mediated ca2+ channel inhibition. 15282155 - A sea urchin egg jelly peptide induces a cgmp-mediated decrease in sperm intracellular ... 8022415 - Insulin-like growth factor-i induces a rapid increase in calcium currents and spontaneo... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-08-05 |
Journal Detail:
|
Title: Circulation research Volume: 107 ISSN: 1524-4571 ISO Abbreviation: Circ. Res. Publication Date: 2010 Oct |
Date Detail:
|
Created Date: 2010-10-01 Completed Date: 2010-10-22 Revised Date: 2010-12-20 |
Medline Journal Info:
|
Nlm Unique ID: 0047103 Medline TA: Circ Res Country: United States |
Other Details:
|
Languages: eng Pagination: 851-9 Citation Subset: IM |
Affiliation:
|
Department of Medicine, University of California, Davis, CA 95616, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Action Potentials
/
physiology* Amino Acid Sequence Animals Cells, Cultured Heart Atria / cytology Humans Mice Molecular Sequence Data Myocytes, Cardiac / cytology, physiology* Patch-Clamp Techniques Potassium / metabolism* Protein Multimerization Protein Structure, Tertiary Small-Conductance Calcium-Activated Potassium Channels* / chemistry, genetics, physiology Transfection |
| Grant Support | |
ID/Acronym/Agency:
|
HL085844/HL/NHLBI NIH HHS; R01 HL075274/HL/NHLBI NIH HHS; R01 HL085727-04/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/KCNN1 protein, human; 0/KCNN2 protein, human; 0/KCNN3 protein, human; 0/Kcnn1 protein, mouse; 0/Kcnn2 protein, mouse; 0/Kcnn3 protein, mouse; 0/Small-Conductance Calcium-Activated Potassium Channels; 7440-09-7/Potassium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Notch3 is critical for proper angiogenesis and mural cell investment.
Next Document: In this issue.