RT info:eu-repo/semantics/article
T1 Kv1.3 channels can modulate cell proliferation during phenotypic switch by an ion-flux independent mechanism
A1 Cidad Velasco, María Del Pilar
A1 Jiménez Pérez, Laura
A1 García Arribas, Daniel
A1 Miguel Velado, Eduardo
A1 Tajada Esteban, Sendoa
A1 Ruiz McDavitt, Christian
A1 López López, José Ramón
A1 Pérez García, María Teresa
K1 Gene expression
K1 Expresión génica
K1 Ion channels
K1 Canales iónicos
K1 Vascular smooth muscle
K1 Músculo liso vascular
K1 Cell proliferation
K1 Proliferación celular
AB Objective: Phenotypic modulation of vascular smooth muscle cells has been associated with a decreased expression of allvoltage-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 musclecells in culture. This study was designed to explore if these changes in Kv1 expression pattern constituted a landmark ofphenotypic modulation across vascular beds and to investigate the mechanisms involved in the proproliferative functionof Kv1.3 channels.Methods and Results: Changes in Kv1.3 and Kv1.5 channel expression were reproduced in mesenteric and aortic vascularsmooth muscle cells, and their correlate with protein expression was electrophysiologicaly confirmed using selectiveblockers. Heterologous expression of Kv1.3 and Kv1.5 channels in HEK cells has opposite effects on the proliferationrate. 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 isactivated 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 targetto control unwanted vascular remodeling.
PB American Heart Association
SN 1524-4636
YR 2012
FD 2012
LK http://uvadoc.uva.es/handle/10324/44607
UL http://uvadoc.uva.es/handle/10324/44607
LA eng
NO Arteriosclerosis, Thrombosis, and Vascular Biology, 2012, vol. 32, n. 5. p. 1299-1307
NO Producción Científica
DS UVaDOC
RD 22-dic-2024