Neurological disorders are increasingly common in older adults, often due to impaired nerve cell function. Researchers from the School of Biological Sciences (SBS) have uncovered new insights into ion channels, providing a deeper understanding of neurological diseases.
From left to right: Manikkoth Balakrishna Asha, Li Zhuowen, Asst. Prof. Sandip Basak, and Nikhil Bharambe
The Role of Ion Channels in Nerve Cell Communication
Nerve cells communicate through electrical signals, a process made possible by ion channels – tiny gateways that control the flow of ions across cell membranes. When these channels malfunction, nerve communication is disrupted, leading to conditions such as epilepsy, anxiety, and Alzheimer’s disease.
Pentameric ligand-gated ion channels (pLGICs) are essential for fast neurotransmission and are key drug targets for neurological disorders. Although their overall structures are known, how these channels change shape during activation has remained unclear because intermediate states are fleeting. Understanding their function is crucial for guiding future drug development.
Peering into Molecular Gates with Cryo-EM
In a study published in Proceedings of the National Academy of Sciences (PNAS) on 23 October 2025, Nanyang Assistant Professor Sandip Basak and his research team explored how ion channels open and close to regulate ion movement. Using the bacterial ion channel GLIC as a model, the team employed cryo-electron microscopy (cryo-EM), a technique offering several thousand times higher magnification than a light microscope, to visualise the protein at near-atomic resolution.
To gain a comprehensive view of the channel’s function, the team collaborated with a computational specialist and an electrophysiologist. Molecular dynamics simulations and electrophysiology experiments linked the observed structures to specific functional roles, while targeted mutations identified key residues involved in gating.
Collaboration Driving Discovery
The study was a team effort, combining structural, computational, and electrophysiological expertise. Key contributors from SBS, including Mr. Li Zhuowen, Dr. Nikhil Bharambe, and Dr. Asha Manikkoth Balakrishna, played pivotal roles in experiments and analysis. Together with Asst. Prof. Sandip Basak, their work revealed molecular details of ion channel behaviour that were previously inaccessible.
This multidisciplinary approach captured asymmetric intermediate states in the homopentameric GLIC channel, showing that even symmetric ion channels can activate through asymmetric pathways – a major insight into PLGIC function.
Implications for Future Treatments
By revealing these previously hidden mechanisms, the study provides a foundation for designing drugs that target ion channels more effectively. These findings could ultimately guide future therapeutic strategies, offering hope for patients with neurological disorders caused by disrupted nerve signalling.
Read the full paper here.