The goal of this project is fluorescently visualize potassium (K+) egress and extracellular accumulation at the cell surface. The development of this innovative technology has the potential to enable the large-scale spatiotemporal resolution of neuronal and glial cell activity. For this project, we are exploiting the presence of the cell's glycocalyx to attach potassium-sensitive fluorophores exactly where K+ accumulates and is reabsorbed by glia. There is one aim to this project: To synthesize a novel, near-IR K+ sensor that covalently modifies the glycocalyces of living cells to fluorescently detect and measure K+ efflux and accumulation. The completion of this aim will yield a transformative set of chemical-biological tools and methodologies to investigate the physiology and pathophysiology of K+ activity in neurons, glia, and potentially in living animals.
The orchestrated release and reabsorption of potassium ions from neurons and glia is essential for neuronal excitability. Accordingly, dysregulated release and absorption of potassium has been linked to multiple sclerosis, epilepsy, migraines, neurodegenerative disorders, and some forms of neuropathic pain. By visualizing the spatiotemporal release and accumulation of potassium in cells, tissues and potentially model mammalian organisms, we aim to understand how these integrated potassium signals regulate brain function in healthy and diseased individuals.
|Bandara, H M Dhammika; Hua, Zhengmao; Zhang, Mei et al. (2017) Palladium-Mediated Synthesis of a Near-Infrared Fluorescent K+ Sensor. J Org Chem 82:8199-8205|