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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

Cidad Velasco, María Del Pilar Jiménez Pérez, Laura García Arribas, Daniel Miguel Velado, Eduardo Tajada Esteban, Sendoa Ruiz McDavitt, Christian López López, José Ramón Pérez García, María Teresa 2020-12-28T13:15:13Z 2020-12-28T13:15:13Z 2012 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 Producción Científica 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. Instituto de Salud Carlos III (grant R006/009) Ministerio de Ciencia, Innovación y Universidades (grant BFU2010-15898) Junta de Castilla y León (grant VA094A11-2) application/pdf eng American Heart Association info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/3.0/ © 2012 American Heart Association Attribution-NonCommercial-NoDerivs 3.0 Unported Gene expression Expresión génica Ion channels Canales iónicos Vascular smooth muscle Músculo liso vascular Cell proliferation Proliferación celular Kv1.3 channels can modulate cell proliferation during phenotypic switch by an ion-flux independent mechanism info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion https://www.ahajournals.org/doi/10.1161/ATVBAHA.111.242727 SI