Key result
Kv1.3 channel expression promotes vascular smooth muscle cell proliferation through a voltage-dependent conformational change independent of ion conduction.
Kv1.3 channels promote vascular smooth muscle cell proliferation through a voltage-dependent conformational change independent of ion conduction, identifying it as a potential target for preventing unwanted vascular remodeling.
May identify a non-conducting Kv1.3 target in remodeling; leaves open translation from animal VSMC models to human disease.
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.
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Cidad et al. (2012) studied Vascular remodeling. Kv1.3 channel expression vs. Kv1.5 channel expression or suppression of voltage-dependence was evaluated on Cell proliferation rate. Kv1.3 channel expression promotes vascular smooth muscle cell proliferation through a voltage-dependent conformational change independent of ion conduction.
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