The voltage-gated K⁺ channel Kv1.3 modulates platelet motility and α₂β₁ integrin-dependent adhesion to collagen

Kv1.3 is a voltage-gated K⁺-selective channel with roles in immunity, insulin-sensitivity, neuronal excitability and olfaction. Despite being one of the largest ionic conductances of the platelet surface membrane, its contribution to platelet function is poorly understood. Here we show that Kv1.3-deficient platelets display enhanced ADP-evoked platelet aggregation and secretion, and an increased surface expression of platelet integrin α_IIb. In contrast, platelet adhesion and thrombus formation <i>in vitro</i> under arterial shear conditions on surfaces coated with collagen were reduced for samples from Kv1.3^−/- compared to wild type mice. Use of collagen-mimetic peptides revealed a specific defect in the engagement with α₂β₁. Kv1.3^−/- platelets developed significantly fewer, and shorter, filopodia than wild type platelets during adhesion to collagen fibrils. Kv1.3^−/- mice displayed no significant difference in thrombus formation within cremaster muscle arterioles using a laser-induced injury model, thus other pro-thrombotic pathways compensate <i>in vivo</i> for the adhesion defect observed <i>in vitro</i>. This may include the increased platelet counts of Kv1.3^−/- mice, due in part to a prolonged lifespan. The ability of Kv1.3 to modulate integrin-dependent platelet adhesion has important implications for understanding its contribution to normal physiological platelet function in addition to its reported roles in auto-immune diseases and thromboinflammatory models of stroke.