# Shaker/Kv1 potassium channel SHK-1 protects against pathogen infection and oxidative stress in C. elegans

## TL;DR

A potassium channel in worms helps protect against infections and stress by maintaining energy and cell function.

## Contribution

SHK-1 protects against pathogens and stress by regulating glycogen, mitochondria, and gene expression in C. elegans.

## Key findings

- shk-1 mutants are highly susceptible to bacterial infection and oxidative stress.
- Reduced glycogen and mitochondrial dysfunction are observed in shk-1 mutants under stress.
- Overexpression of catp-3 rescues mitochondrial membrane potential and stress tolerance in shk-1 mutants.

## Abstract

The Shaker/Kv1 subfamily of voltage-gated potassium (K+) channels is essential for modulating membrane excitability. Their loss results in prolonged depolarization and excessive calcium influx. These channels have also been implicated in a variety of other cellular processes, but the underlying mechanisms remain poorly understood. Through comprehensive screening of K+ channel mutants in C. elegans, we discovered that shk-1 mutants are highly susceptible to bacterial pathogen infection and oxidative stress. This vulnerability is associated with reduced glycogen levels and substantial mitochondrial dysfunction, including decreased ATP production and dysregulated mitochondrial membrane potential under stress conditions. SHK-1 is predominantly expressed and functions in body wall muscle to maintain glycogen storage and mitochondrial homeostasis. RNA-sequencing data reveal that shk-1 mutants have decreased expression of a set of cation-transporting ATPases (CATP), which are crucial for maintaining electrochemical gradients. Intriguingly, overexpressing catp-3, but not other catp genes, restores the depolarization of mitochondrial membrane potential under stress and enhances stress tolerance in shk-1 mutants. This finding suggests that increased catp-3 levels may help restore electrochemical gradients disrupted by shk-1 deficiency, thereby rescuing the phenotypes observed in shk-1 mutants. Overall, our findings highlight a critical role for SHK-1 in maintaining stress tolerance by regulating glycogen storage, mitochondrial homeostasis, and gene expression. They also provide insights into how Shaker/Kv1 channels participate in a broad range of cellular processes.

Exposure to environmental stimuli, such as bacterial pathogens, increases the production of reactive oxygen species (ROS), leading to oxidative stress and widespread cellular damage. Cells employ various defense mechanisms to counteract ROS-induced damages and maintain cellular homeostasis. In this study, we found that the Shaker/Kv1 channel SHK-1, typically known for its regulation of membrane excitability, also helps protect C. elegans against bacterial infections and oxidative stress. Animals lacking shk-1 are highly sensitive to pathogens and prooxidant exposure, and show defects in gene expression, glycogen storage, and mitochondrial function. Notably, shk-1 mutants have reduced expression of catp-3, encoding one of cation-transporting ATPases that are critical for maintaining ion balance. Restoring catp-3 expression rescues the defects observed in shk-1-deficient animals, suggesting that the loss of SHK-1 likely disturbs ion homeostasis, which can be mitigated by increased levels of catp-3. These findings offer a new perspective on the fundamental mechanism by which SHK-1 regulates diverse cellular functions. Moreover, our observations may have implications for how Kv1.3 is involved in various physiological processes in mammals.