Cholesterol depletion increases sodium currents mediated by Nav1.7

Cholesterol is a crucial component of cellular membranes. In our latest study in cooperation with Giulia Rossetti, we explored the impact of cholesterol depletion on Nav1.7, a key ion channel found primarily in peripheral neurons, which plays a significant role in transmitting pain signals. Our findings, published in the International Journal of Biological Macromolecules, reveal that reducing membrane cholesterol significantly alters the behavior of Nav1.7, leading to an increase in current densities and changes in fast inactivation.

The study combined molecular dynamics (MD) simulations and their validation in a laboratory setting using HEK293t cells expressing Nav1.7. We used whole-cell patch clamp to demonstrate that cholesterol depletion could potentially induce hyperexcitability-like phenotypes.

Thank you to all authors: Simone Albani (Rossetti group) and Vishal Eswaran (Lampert group) leading the study, Alessia Piergentili, Paulo Cesar Telles de Souza, and Giulia Rossetti.

Reference:  ALBANI*, Simone, ESWARAN*, Vishal, et al. Depletion of membrane cholesterol modifies structure, dynamic and activation of Nav1. 7. International Journal of Biological Macromolecules, 2024, S. 134219.