Peptide Lv Promotes Trafficking and Membrane Insertion of K(Ca)3.1 through the MEK1-ERK and PI3K-Akt Signaling Pathways

卷:12

Article

关键词: K-CA CHANNELS;    INTERMEDIATE-CONDUCTANCE;    HYPERPOLARIZING FACTOR;    ENDOTHELIAL-CELL;    NITRIC-OXIDE;    DEPENDENT ACTIVATION;    ANGIOGENESIS;    VEGF;    AKT;    EDHF;   

DOI  :  10.3390/cells12121651

来源: SCIE

【 摘 要 】

Peptide Lv is a small endogenous secretory peptide that is proangiogenic through hyperpolarizing vascular endothelial cells (ECs) by enhancing the current densities of K(Ca)3.1 channels. However, it is unclear how peptide Lv enhances these currents. One way to enhance the current densities of ion channels is to promote its trafficking and insertion into the plasma membrane. We hypothesized that peptide Lv-elicited K(Ca)3.1 augmentation occurs through activating the mitogen-activated protein kinase kinase 1 (MEK1)-extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt) signaling pathways, which are known to mediate ion channel trafficking and membrane insertion in neurons. To test this hypothesis, we employed patch-clamp electrophysiological recordings and cell-surface biotinylation assays on ECs treated with peptide Lv and pharmaceutical inhibitors of ERK and Akt. Blocking ERK or Akt activation diminished peptide Lv-elicited EC hyperpolarization and increase in K(Ca)3.1 current densities. Blocking PI3K or Akt activation decreased the level of plasma membrane-bound, but not the total amount of K(Ca)3.1 protein in ECs. Therefore, the peptide Lv-elicited EC hyperpolarization and K(Ca)3.1 augmentation occurred in part through channel trafficking and insertion mediated by MEK1-ERK and PI3K-Akt activation. These results demonstrate the molecular mechanisms of how peptide Lv promotes EC-mediated angiogenesis.