The calcium‐activated potassium channel KCa3.1 plays a central role in the chemotactic response of mammalian neutrophils. (19th July 2015)

• Record Type: Journal Article
• Authors: Henríquez, C.; Riquelme, T. T.; Vera, D.; Julio‐Kalajzić, F.; Ehrenfeld, P.; Melvin, J. E.; Figueroa, C. D.; Sarmiento, J.; Flores, C. A.
• Is Part Of: Acta physiologica. Volume 216:Number 1(2016)
• Page Start: 132
• Page End: 145
• Publication Date: 2015-07-19
• Subjects: chemotaxis -- KCa3.1 -- neutrophil; Physiology -- Periodicals; Physiology -- Research -- Periodicals; 612
• DOI: 10.1111/apha.12548
• Languages: English
• ISSNs: 1748-1708

Abstract

Abstract: Aim: Neutrophils are the first cells to arrive at sites of injury. Nevertheless, many inflammatory diseases are characterized by an uncontrolled infiltration and action of these cells. Cell migration depends on volume changes that are governed by ion channel activity, but potassium channels in neutrophil have not been clearly identified. We aim to test whether KCa3.1 participates in neutrophil migration and other relevant functions of the cell. Methods: Cytometer and confocal measurements to determine changes in cell volume were used. Cells isolated from human, mouse and horse were tested for KCa3.1‐dependent chemotaxis. Chemokinetics, calcium handling and release of reactive oxygen species were measured to determine the role of KCa3.1 in those processes. A mouse model was used to test for neutrophil recruitment after acute lung injury in vivo . Results: We show for the first time that KCa3.1 is expressed in mammalian neutrophils. When the channel is inhibited by a pharmacological blocker or by genetic silencing, it profoundly affects cell volume regulation, and chemotactic and chemokinetic properties of the cells. We also demonstrated that pharmacological inhibition of KCa3.1 did not affect calcium entry or reactive oxygen species production in neutrophils. Using a mouse model of acute lung injury, we observed that Kca3.1 −/− mice are significantly less effective at recruiting neutrophils into the site of inflammation. Conclusions: These results demonstrate that KCa3.1 channels are key actors in the migration capacity of neutrophils, and its inhibition did not affect other relevant cellular functions.