Document Detail


Cell cycle-dependent expression of Kv3.4 channels modulates proliferation of human uterine artery smooth muscle cells.
MedLine Citation:
PMID:  20093253     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIMS: Vascular smooth muscle cell (VSMC) proliferation is involved in cardiovascular pathologies associated with unwanted arterial wall remodelling. Coordinated changes in the expression of several K+ channels have been found to be important elements in the phenotypic switch of VSMCs towards proliferation. We have previously demonstrated the association of functional expression of Kv3.4 channels with proliferation of human uterine VSMCs. Here, we sought to gain deeper insight on the relationship between Kv3.4 channels and cell cycle progression in this preparation. METHODS AND RESULTS: Expression and function of Kv3.4 channels along the cell cycle was explored in uterine VSMCs synchronized at different checkpoints, combining real-time PCR, western blotting, and electrophysiological techniques. Flow cytometry, Ki67 expression and BrdU incorporation techniques allowed us to explore the effects of Kv3.4 channels blockade on cell cycle distribution. We found cyclic changes in Kv3.4 and MiRP2 mRNA and protein expression along the cell cycle. Functional studies showed that Kv3.4 current amplitude and Kv3.4 channels contribution to cell excitability increased in proliferating cells. Finally, both Kv3.4 blockers and Kv3.4 knockdown with siRNA reduced the proportion of proliferating VSMCs. CONCLUSION: Our data indicate that Kv3.4 channels exert a permissive role in the cell cycle progression of proliferating uterine VSMCs, as their blockade induces cell cycle arrest after G2/M phase completion. The modulation of resting membrane potential (V(M)) by Kv3.4 channels in proliferating VSMCs suggests that their role in cell cycle progression could be at least in part mediated by their contribution to the hyperpolarizing signal needed to progress through the G1 phase.
Authors:
Eduardo Miguel-Velado; Francisco D P?rez-Carretero; Olaia Colinas; Pilar Cidad; Magda Heras; Jos? R L?pez-L?pez; M Teresa P?rez-Garc?a
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-01-21
Journal Detail:
Title:  Cardiovascular research     Volume:  86     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-13     Completed Date:  2010-06-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  383-91     Citation Subset:  IM    
Affiliation:
Departamento de Bioqu?mica y Biolog?a Molecular y Fisiolog?a e Instituto de Biolog?a y Gen?tica Molecular , Universidad de Valladolid y CSIC, Valladolid, Spain.
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MeSH Terms
Descriptor/Qualifier:
Cell Cycle* / drug effects,  genetics
Cell Proliferation* / drug effects
Cells, Cultured
Female
Humans
Membrane Potentials
Muscle, Smooth, Vascular / drug effects,  metabolism*
Myocytes, Smooth Muscle / drug effects,  metabolism*
Phenotype
Potassium Channel Blockers / pharmacology
Potassium Channels, Voltage-Gated / genetics,  metabolism
RNA Interference
RNA, Messenger / metabolism
Shaw Potassium Channels / antagonists & inhibitors,  genetics,  metabolism*
Signal Transduction
Uterine Artery / metabolism
Chemical
Reg. No./Substance:
0/KCNC4 protein, human; 0/KCNE3 protein, human; 0/Potassium Channel Blockers; 0/Potassium Channels, Voltage-Gated; 0/RNA, Messenger; 0/Shaw Potassium Channels
Comments/Corrections
Comment In:
Cardiovasc Res. 2010 Jun 1;86(3):351-2   [PMID:  20378681 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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