Abstract

The Sodium-Calcium Exchanger (NCX) is a critical membrane protein responsible for maintaining intracellular calcium homeostasis, particularly in excitable cells like neurons. Dysregulation of NCX activity is implicated in various neurological and cardiac pathologies. This study investigates the pharmacological sensitivity of NCX transport currents to lithium ions and selective NCX inhibitors in two distinct cellular environments: primary neuronal cultures and human embryonic kidney (HEK293) cells. Using whole-cell patch-clamp electrophysiology, we characterized the NCX-mediated currents under varying ionic conditions. Our results demonstrate that lithium acts as a potent modulator, significantly altering the magnitude and kinetics of the outward NCX current, suggesting a complex interaction with the ion binding sites. Furthermore, selective inhibitors exhibited differential efficacy between the neuronal and HEK293 cell lines, highlighting potential cell-specific regulatory mechanisms or isoform variations. These findings provide crucial insights into the pharmacological profile of the NCX, which is essential for developing targeted therapeutic strategies for conditions involving calcium dysregulation.