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.
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.
Authors: Laura Jiménez-Pérez; Pilar Cidad; Inés Álvarez-Miguel; Alba Santos-Hipólito; Rebeca Torres-Merino; Esperanza Alonso; Miguel Ángel de la Fuente; José Ramón López-López; M Teresa Pérez-García Journal: J Biol Chem Date: 2015-12-10 Impact factor: 5.157
Authors: Špela Gubič; Louise A Hendrickx; Žan Toplak; Maša Sterle; Steve Peigneur; Tihomir Tomašič; Luis A Pardo; Jan Tytgat; Anamarija Zega; Lucija P Mašič Journal: Med Res Rev Date: 2021-05-01 Impact factor: 12.944
Authors: Sanjeev Kumar Upadhyay; Kristin L Eckel-Mahan; M Reza Mirbolooki; Indra Tjong; Stephen M Griffey; Galina Schmunk; Amanda Koehne; Briac Halbout; Shawn Iadonato; Brian Pedersen; Emiliana Borrelli; Ping H Wang; Jogeshwar Mukherjee; Paolo Sassone-Corsi; K George Chandy Journal: Proc Natl Acad Sci U S A Date: 2013-05-31 Impact factor: 11.205