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oai:uvadoc.uva.es:10324/446072024-12-16T09:15:04Zcom_10324_1134com_10324_931com_10324_894com_10324_32522com_10324_952com_10324_43677com_10324_954col_10324_1213col_10324_32523col_10324_43678

00925njm 22002777a 4500 dc Cidad Velasco, María Del Pilar author Jiménez Pérez, Laura author García Arribas, Daniel author Miguel Velado, Eduardo author Tajada Esteban, Sendoa author Ruiz McDavitt, Christian author López López, José Ramón author Pérez García, María Teresa author 2012 Objective: Phenotypic modulation of vascular smooth muscle cells has been associated with a decreased expression of all voltage-dependent potassium channel (Kv)1 channel encoding genes but Kcna3 (which encodes Kv1.3 channels). In fact, upregulation of Kv1.3 currents seems to be important to modulate proliferation of mice femoral vascular smooth muscle cells in culture. This study was designed to explore if these changes in Kv1 expression pattern constituted a landmark of phenotypic modulation across vascular beds and to investigate the mechanisms involved in the proproliferative function of Kv1.3 channels. Methods and Results: Changes in Kv1.3 and Kv1.5 channel expression were reproduced in mesenteric and aortic vascular smooth muscle cells, and their correlate with protein expression was electrophysiologicaly confirmed using selective blockers. Heterologous expression of Kv1.3 and Kv1.5 channels in HEK cells has opposite effects on the proliferation rate. The proproliferative effect of Kv1.3 channels was reproduced by “poreless” mutants but disappeared when voltagedependence of gating was suppressed. Conclusion: These findings suggest that the signaling cascade linking Kv1.3 functional expression to cell proliferation is activated by the voltage-dependent conformational change of the channels without needing ion conduction. Additionally, the conserved upregulation of Kv1.3 on phenotypic modulation in several vascular beds makes this channel a good target to control unwanted vascular remodeling. Arteriosclerosis, Thrombosis, and Vascular Biology, 2012, vol. 32, n. 5. p. 1299-1307 1524-4636 http://uvadoc.uva.es/handle/10324/44607 10.1161/ATVBAHA.111.242727 Kv1.3 channels can modulate cell proliferation during phenotypic switch by an ion-flux independent mechanism