Published online before print November 3, 2005, doi: 10.1161/01.RES.0000194322.91255.13
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Submitted on August 5, 2005
Revised on October 19, 2005
Accepted on October 20, 2005
Contribution of Kv Channels to Phenotypic Remodeling of Human Uterine Artery Smooth Muscle Cells
Eduardo Miguel-Velado ;
From the Departamento de Bioquímica y Biología Molecular y Fisiología e Instituto de Biología y Genética Molecular (E.M.-V., A.M.-D., O.C., P.C., M.T.P.-G., J.R.L.-L.), Universidad de Valladolid y Consejo Superior de Investigaciones Científicas, Facultad de Medicina, Valladolid, Spain; and Institut de Malalties Cardiovasculars (M.H.), Hospital Clinic, Institut d’Investigacions Biomediques August Pi i Sunyer, Universidad de Barcelona, Barcelona, Spain.
* To whom correspondence should be addressed. E-mail: jrlopez{at}ibgm.uva.es.
Vascular smooth muscle cells (VSMCs) perform diverse functions that can be classified into contractile and synthetic (or proliferating). All of these functions can be fulfilled by the same cell because of its capacity of phenotypic modulation in response to environmental changes. The resting membrane potential is a key determinant for both contractile and proliferating functions. Here, we have explored the expression of voltage-dependent K+ (Kv) channels in contractile (freshly dissociated) and proliferating (cultured) VSMCs obtained from human uterine arteries to establish their contribution to the functional properties of the cells and their possible participation in the phenotypic switch. We have studied the expression pattern (both at the mRNA and at the protein level) of Kv
subunits in both preparations as well as their functional contribution to the K+ currents of VSMCs. Our results indicate that phenotypic remodeling associates with a change in the expression and distribution of Kv channels. Whereas Kv currents in contractile VSMCs are mainly performed by Kv1 channels, Kv3.4 is the principal contributor to K+ currents in cultured VSMCs. Furthermore, selective blockade of Kv3.4 channels resulted in a reduced proliferation rate, suggesting a link between Kv channels expression and phenotypic remodeling.
Key words: Kv channel expression • vascular smooth muscle cells • cell proliferation • K+ currents
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