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, Pilar
A1 Jiménez-Pérez, Laura
A1 García-Arribas, Daniel
A1 Miguel-Velado, Eduardo
A1 Tajada, Sendoa
A1 Ruiz-McDavitt, Christian
A1 López-López, José R.
A1 Pérez-García, M. Teresa
AB 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 voltage-dependence of gating was suppressed.Conclusions: 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.
SN 1079-5642
YR 2012
FD 2012
LK https://uvadoc.uva.es/handle/10324/65779
UL https://uvadoc.uva.es/handle/10324/65779
LA spa
NO Arterioscler Thromb Vasc Biol. 2012 May;32(5):1299-307.
DS UVaDOC
RD 29-nov-2024