RT info:eu-repo/semantics/article
T1 Cell cycle-dependent expression of Kv3.4 channels modulates proliferation of human uterine artery smooth muscle cells
A1 Miguel Velado, Eduardo
A1 Pérez Carretero, Francisco D.
A1 Colinas, Olaia
A1 Cidad Velasco, María Del Pilar
A1 Heras i Fortuny, Maria Magdalena
A1 López López, José Ramón
A1 Pérez García, María Teresa
K1 Vascular smooth muscle
K1 Músculo liso vascular
K1 Potassium channels
K1 Canales de potasio
K1 Cell proliferation
K1 Proliferación celular
K1 Electrophysiology
K1 Electrofisiología
K1 32 Ciencias Médicas
AB 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 (VM) 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.
PB Oxford University Press
SN 1755-3245
YR 2010
FD 2010
LK http://uvadoc.uva.es/handle/10324/44597
UL http://uvadoc.uva.es/handle/10324/44597
LA eng
NO Cardiovascular Research, 2010, vol. 86, n. 3. p. 383-391
NO Producción Científica
DS UVaDOC
RD 22-dic-2024