Functional interactions of Kv1.3 channels in microglia and T cells and their implications in neurodegeneration

Kv1.3 is a voltage-gated potassium channel expressed on immune cells. It functions in coordination with calcium channels to maintain cellular homeostasis. Several studies support important roles for Kv1.3 in microglia-driven neuroinflammation and T cell-mediated autoimmunity. Based on recent evidence, Kv1.3 may regulate immune functions via its protein-protein interactions, which vary with cell type and cell state. In this review, we summarize Kv1.3 channel's overlapping as well as distinct functions in microglia and T cells. Using network analysis of existing Kv1.3 interactomes and human brain and genetic datasets, we nominate Kv1.3-associated mechanisms in Alzheimer's disease (AD). With the emerging roles for innate (microglia) and adaptive (T cell) mechanisms in AD, and the known expression patterns of Kv1.3 channels in given cell types, we propose that Kv1.3 represents a target to modulate both facets of neuroinflammation in AD. Accordingly, we emphasize the need for future myeloid- and T cell-specific mechanistic studies on Kv1.3.