Fig. 7: Diagrammatic representation of the proposed mechanism for Kv1.3-induced respiration and proliferation.

Kv1.3 channels potentially located at the mitochondria require voltage sensing and an intact ERK1/2 phosphorylation site (Y447) to stimulate mitochondrial oxidative phosphorylation. Kv1.3-induced oxidative phosphorylation drives increased ATP turnover, meeting the increased energy demands needed for proliferation. Simultaneously, Kv1.3-induced oxidative phosphorylation generates mitochondrial reactive oxygen species (ROS) which stimulate the proliferative phenotype of the cells. This process is independent of plasma membrane Kv1.3 channel ion conductance. However, it may be speculated that growth factor receptors at the cell plasma membrane may signal to Kv1.3 channels via downstream ERK1/2-mediated phosphorylation.