Beyond ion flux: the potassium channel KV1.3 and its regulatory function in neutrophils

The voltage-gated potassium channel K V 1.3 (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, K V 1.3 has been postulated to exert additional functions in immune biology. In this review, we summarize how recruitment of K V 1.3 into cholesterol-rich lipid raft microdomains positions K V 1.3 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 K V 1.3 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 K V 1.3 interactomics and spatiotemporal raft/adhesion nanodomain mapping. • K V 1.3 regulates neutrophil effector functions. • K V 1.3 links ion flux to immune signaling. • K V 1.3 acts as a scaffold for kinases, adaptors, and transcriptional regulators. • K V 1.3 localizes within lipid rafts and may serve as a signaling hub in neutrophils. • K V 1.3 represents a therapeutic target for neutrophil-driven inflammation.