Pharmacological activator of Piezo1 mechanosensitive channels induces increased stiffness of sensory neurons
DOI:
https://doi.org/10.33910/2687-1270-2024-5-4-336-344Keywords:
sensory neurons, atomic force microscopy, Piezo1 channels, Jedi2, organotypic tissue cultureAbstract
Mechanosensitive ion channels of the Piezo family, discovered in 2010, are crucial participants of intracellular mechanotransduction. The Piezo1 and Piezo2 channels are found in various cell types, including primary sensory neurons, although their precise roles remain poorly understood. Although Jedi2, a pharmacological activator of Piezo1 channels, has been shown to modulate Piezo1 activity, its effects on neurons have not been studied yet. In this work, we investigate the impact of Jedi2 on primary sensory neurons. Using organotypic tissue culture, we demonstrate that Jedi2 regulates neurite growth of sensory neurons of dorsal root ganglia in a dose-dependent manner. Atomic force microscopy revealed that a 10 μM concentration of Jedi2 — while having no effect on neurite growth — induces a significant increase in the stiffness of primary sensory neurons. This response can be explained by the triggering of intracellular Ca2+-dependent signaling pathways mediated by Piezo1 channel activation. Our findings suggest that Jedi2 at 10 μM concentration can serve as a useful tool for exploring the molecular mechanisms of Piezo1- mediated mechanotransduction in primary sensory neurons under physiologically relevant conditions.
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