John Ku , Hans-Joachim Anders , Markus Sperandio and Roland Immler
Abstract
The voltage-gated potassium channel KV1.3 (KCNA3) is a critical ion channel regulating membrane potential in immune cells, facilitating sustained calcium influx and activating downstream signaling events. Besides its canonical role as an ion channel, KV1.3 has been postulated to exert additional functions in immune biology. In this review, we summarize how recruitment of KV1.3 into cholesterol-rich lipid raft microdomains positions KV1.3 as a scaffold (demonstrated directly in T cells and microglia) for kinases, adaptor proteins, and transcriptional regulators, integrating ion flux with receptor signaling pathways that control adhesion, migration, and damage-associated molecular pattern release in immune cells. We further discuss how these observations may explain recent findings in KV1.3 function in neutrophil biology and how its inhibition may offer a refined strategy to selectively modulate immune responses in sterile inflammation and beyond. This highlights the need for neutrophil-specific KV1.3 interactomics and spatiotemporal raft/adhesion nanodomain mapping.
