Vascular smooth muscle cells (VSMCs) of mature animals are highly specialized cells whose main function is contraction of blood vessels. However, VSMCs maintain great plasticity, being capable of switching from a contractile (freshly dissociated) to an activated-proliferating (cultured) phenotype in response to local environmental changes. Voltage-dependent K⁺ channels (Kv channels) are principal determinants of vascular tone by controlling membrane potential, as well as intracellular pH and cell volume. We have studied the expression pattern of Kva subunits in contractile and proliferating VSMCs from uterine arteries and we have determined their functional contribution to cell excitability. We found that the electrical remodelling associated to phenotypic changes involves an increase in Kv3.4 mRNA expression and a translocation of the protein from intracellular locations to the plasma membrane. Selective blockade of Kv3.4 channels in proliferating VSMCs leads to a decreased proliferation rate, while blockade of proliferation (by maintaining the cells in a serum- and grow factors-free medium) decreases the expression levels of Kv3.4 mRNA. Moreover, functional blockade and over-expression experiments (by transfecting VSMCs with Kv3.4 plasmid or Kv3.4 siRNA respectively) suggest a correlation between the expression level of Kv3.4 and migratory and proliferating activity of the cells. Altogether, our data demonstrate a link between Kv3.4 channel expression and phenotypic remodelling, providing a new role for this ion channel in proliferating and migratory processes in VSMCs. Supported by ISCIII grants R006/009 (Red Heracles) and PI041044, MEC grant BFU2004-05551 and JCyL grant VA011C05