Contribution of Kv channels to phenotypic remodeling of human uterine artery smooth muscle cells.
Vascular smooth muscle cells (VSMCs) perform diverse functions that can be classified into contractile and synthetic (or proliferating). All of these functions can be fulfilled by the same cell because of its capacity of phenotypic modulation in response to environmental changes. The resting membrane potential is a key determinant for both contractile and proliferating functions. Here, we have explored the expression of voltage-dependent K+ (Kv) channels in contractile (freshly dissociated) and proliferating (cultured) VSMCs obtained from human uterine arteries to establish their contribution to the functional properties of the cells and their possible participation in the phenotypic switch. We have studied the expression pattern (both at the mRNA and at the protein level) of Kvalpha subunits in both preparations as well as their functional contribution to the K+ currents of VSMCs. Our results indicate that phenotypic remodeling associates with a change in the expression and distribution of Kv channels. Whereas Kv currents in contractile VSMCs are mainly performed by Kv1 channels, Kv3.4 is the principal contributor to K+ currents in cultured VSMCs. Furthermore, selective blockade of Kv3.4 channels resulted in a reduced proliferation rate, suggesting a link between Kv channels expression and phenotypic remodeling.
Miguel-Velado
Eduardo
E
Departamento de Bioquímica y Biología Molecular y Fisiología, Instituto de Biología y Genética, Universidad de Valladolid, Facultad de Medicina, Consejo Superior de Investigaciones Científicas, Valladolid, Spain.
Moreno-Domínguez
Alejandro
A
Colinas
Olaia
O
Cidad
Pilar
P
Heras
Magda
M
Pérez-García
M Teresa
MT
López-López
José Ramón
JR
D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D010641:Phenotype; D024642:Potassium Channels, Voltage-Gated / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D021122:Protein Subunits; D012333:RNA, Messenger / Q000032:analysis; D051637:Shaker Superfamily of Potassium Channels / Q000187:drug effects / Q000502:physiology; D051672:Shal Potassium Channels / Q000032:analysis / Q000235:genetics; D051670:Shaw Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014315:Triterpenes / Q000494:pharmacology; D014599:Uterus / Q000098:blood supply*
C492015:KCNC4 protein, human; D051036:Large-Conductance Calcium-Activated Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D012333:RNA, Messenger; D051637:Shaker Superfamily of Potassium Channels; D051672:Shal Potassium Channels; D051670:Shaw Potassium Channels; D013757:Tetraethylammonium Compounds; D014315:Triterpenes; C118657:correolide