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

Wright, JR, Jones, S ORCID logoORCID: https://orcid.org/0000-0001-8154-3928, Parvathy, S, Kaczmarek, LK, Forsythe, I, Farndale, RW, Gibbins, JM and Mahaut-Smith, MP (2022) The voltage-gated K+ channel Kv1.3 modulates platelet motility and α2β1 integrin-dependent adhesion to collagen. Platelets, 33 (3). pp. 451-461. ISSN 0953-7104

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Abstract

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 αIIb. In contrast, platelet adhesion and thrombus formation in vitro 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 in vivo for the adhesion defect observed in vitro. 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.

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