Voltage-dependent potassium channel regulatory subunits in the immune system

The immune system depends on ion channels to control activation and maintain cellular homeostasis. The role of voltage-dependent potassium channels (Kv) in immune cells has been well studied in recent decades, with a special interest in the role of Kv1.3 in cell physiology and its implications in autoimmune diseases. However, native K⁺ currents in leukocytes result not only from the assembly of pore-forming α-subunits but are also shaped by regulatory β-subunits that fine-tune gating, trafficking, and pharmacology. Immune cells express members of the Kvβ, KCNE, and KChIP families, but the contribution of these regulatory subunits to immune physiology remains largely underexplored. In this review, we synthesize evidence for regulatory subunit expression and function in leukocytes, focusing on how these partners modify Kv channel behavior and downstream signaling. We highlight Kv1.3-Kvβ2.1-KCNE4 as a promising immunoregulatory complex, and we discuss the role of KChIPs in shaping gene expression as well as a Kv regulatory subunit. Despite gaps in the expression of regulatory subunits in immune cells, increasing evidence highlights the importance of further studies addressing the role of Kvβ-subunits in the immune context. Understanding how Kv channels are regulated in leukocytes could lead to new ways to control immune responses and develop new targeted therapies.