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

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

Authors :
Wright, Joy R
Jones, Sarah
Parvathy, Sasikumar
Kaczmarek, Leonard K
Forsythe, Ian
Farndale, Richard W
Gibbins, Jonathan M
Mahaut-Smith, Martyn P
Source :
Platelets; 2022, Vol. 33 Issue 3, p451-461, 11p
Publication Year :
2022

Abstract

Kv1.3 is a voltage-gated K<superscript>+</superscript>-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<subscript>IIb</subscript>. 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<superscript>−/-</superscript> compared to wild type mice. Use of collagen-mimetic peptides revealed a specific defect in the engagement with α<subscript>2</subscript>β<subscript>1</subscript>. Kv1.3<superscript>−/-</superscript> platelets developed significantly fewer, and shorter, filopodia than wild type platelets during adhesion to collagen fibrils. Kv1.3<superscript>−/-</superscript> 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<superscript>−/-</superscript> 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
09537104
Volume :
33
Issue :
3
Database :
Complementary Index
Journal :
Platelets
Publication Type :
Academic Journal
Accession number :
155780855
Full Text :
https://doi.org/10.1080/09537104.2021.1942818