Inwardly rectifying potassium channels promote directional sensing during neutrophil chemotaxis

TL;DR

Inwardly rectifying potassium channels help neutrophils sense direction during migration, revealing a new role for bioelectricity in immune cell movement.

Contribution

The study identifies a novel role of Kir7.1 channels in directional sensing during neutrophil chemotaxis through membrane potential regulation.

Findings

Blocking or knocking out Kir channels in neutrophils disrupts directional sensing toward chemoattractants.

Kir7.1 is required for depolarization toward chemokine sources in zebrafish neutrophils.

Membrane potential acts as a key component in guiding immune cell migration through feedforward mechanisms.

Abstract

Wang et al. demonstrate that inward-rectifying potassium channels maintain the resting membrane potential and are required for directional sensing during neutrophil chemotaxis. It is a novel molecular mechanism by which bioelectricity regulates cell migration without affecting overall cell motility. The work is significant, given the high importance of immune cell migration in health and disease.

Potassium channels control membrane potential and various physiological processes, including cell migration. However, the specific role of inwardly rectifying potassium channels in immune cell chemotaxis remains unknown. Here, we demonstrate that inwardly rectifying potassium channels, particularly Kir7.1 (Kcnj13), maintain the resting membrane potential and are crucial for directional sensing during neutrophil chemotaxis. Blocking or knocking out Kir in neutrophils disrupted their ability to sense direction toward different chemoattractants in multiple models. Using genetically encoded voltage indicators, we observed oscillating hyperpolarization during tail retraction in zebrafish neutrophils, with Kir7.1 required for depolarization toward the chemokine source. Focal depolarization via optogenetics biased pseudopod selection and triggered new protrusions, which depended on Gα signaling. Global hyperpolarization caused neutrophils to stall migration. Additionally, Kir influences GPCR signaling activation in dHL-60 cells. This research introduces membrane potential as a key component of the complex feedforward mechanism that links the adaptive and excitable networks necessary to guide immune cells in challenging tissue environments.

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