Potassium ion (K+) homeostasis and dynamics play critical roles in all biological systems and particularly in the brain. There's a need to methods that can non invasively and accurately monitor changes of K+ balances as they would non only provide vital information on the basic mechanisms regulating K+ homeostasis at single cell resolution but also benefit disease diagnoses as well as offer insight to pathologies. In this interdisciplinary project gathering chemists and neurophysiologists, we aim to develop new optical calixarene rhodamine-derived chemosensors through rational synthesis for detecting K+ at physiologically relevant concentrations in vitro and in cells. We will conduct physiological experiments in both cultured primary neurons and brain slices to test these new indicators and address how extracellular K+ is regulated under physiological and pathological conditions. Our project will fill a need for the biomedical community in various fields.