The diversity of vascular smooth muscle cells (VSMCs) functions requires different cell phenotypes. For that reason VSMCs are not terminally differentiated, but retain a high degree of plasticity and are able to switch from a contractile to a proliferative and secretory phenotype. This process, known as phenotypic switch, is central to neointimal formation, which constitutes a common pathological lesion in diverse cardiovascular diseases, including coronary heart diseases, postangioplasty restenosis, and transplantation arteriopathy. Phenotypic modulation of VSMCs requires a dramatic change in gene expression profile. An important element in this change is the switch in ion transport mechanisms, as they represent a fundamental system required to redirect cell machinery to new functional tasks. The heterogeneity of ion channels expression pattern across different vascular beds has provided a large number of candidates implicated in the phenotypic switch, but only some of them have been found to be conserved in different VSMCs preparations. In order to circumvent this limitation, we have obtained a global portrait of ion channel expression in contractile versus proliferating mouse femoral arteries VSMCs by using high-throughput real-time PCR. We analyzed the expression of 90 ion channel genes in two experimental paradigms: an in vivo model of endoluminal lesion and an in vitro model of cultured VSMCs obtained from explants. BPN mice (Jackson laboratories) were housed under temperature-controlled conditions (21°C) with free access to water and food. Endoluminal lesion of the common femoral artery was performed as previously described1 in mice anesthetized using isoflurane inhalation (0.5-1% at 2.5 l O2 min-1). To collect arterial samples mice were killed by decapitation after isofluorane anesthesia. All animal protocols were approved by our Institutional Care and Use Committee, and are in accordance with the European Community guiding principles in the care and use of animals. Changes in mRNA expression showed a good correlation between the two proliferative models, with only two genes, Kv1.3 and Kvbeta2, increasing their expression upon proliferation. These mRNA changes translate into similar changes in protein expression levels in both proliferation models. While in contractile VSMCs Kv1.5-mediated currents are predominant, in proliferating VSMCs there is a net increase in the Kv1-mediated component of the Kv current due to the up-regulation of Kv1.3 channels2. Besides, functional studies demonstrate that the up-regulation of Kv1.3 currents in these cells is an essential component of their migratory and proliferative phenotype. As the increased expression of Kv1.3 channels has also been described in proliferating VSMCs from human saphenous veins3, we explored whether this Kv1.3 up-regulation is a conserved landmark of VSMCs proliferation in different vascular beds, as this will point to these channels as good therapeutical targets to avoid unwanted VSMC remodelling. We have analyzed VSMCs from different vascular beds and different species, including human samples, and in all cases we found a predominant expression of Kv1.3 channels in the proliferative phenotype. Moreover, the selective blockade of Kv1.3 currents produced a significant decreased of VSMCs proliferation rate in all the preparations studied. Finally, we have been able to reproduce the pro-proliferative effect of Kv1.3 in a heterologous expression system. This system is becoming a useful tool as it provides a good preparation to explore the molecular determinants and the signalling cascade linking the functional expression of Kv1.3 channels to cell proliferation.