Automated electrophysiology platforms measure the movement of electrical charge associated with ion channel or electrogenic transporter activity. However, chloride homeostasis in the central nervous system that underlies fast inhibitory neurotransmission depends on chloride transporters that include non-electrogenic types that are associated with no net charge movement. Assaying the native function of these transporters is challenging, but can be accomplished by indirect electrophysiological approaches already demonstrated by manual patch-clamp studies. Whether these approaches are amenable to the higher-throughput automated electrophysiological platforms used in drug discovery is unknown. We piloted a feasibility study on the QPatch HTX automated electrophysiology platform. Conceptually, the assay relies on co-transfection of a ligand-gated chloride channel as a means to determine the chloride equilibrium potential (ECl), and hence deduce intracellular chloride concentrations. By driving the transporter in forward and reverse directions through modulation of the extracellular ionic gradients, and determining ECl during this process, it is possible to calculate transporter rates. Key challenges to creating an automated platform assay include the requirement to use weakly-effective gramicidin as perforating agent and balancing the large chloride flux through the ligand-gated channel compared to the much smaller chloride flux carried by the transporter. The results of this proof-of-concept study demonstrated transporter-driven changes in calculated intracellular chloride concentrations of at least 28mM in a transfected cell line, representing a rate of approximately 13mM/min during influx. Overall, this study shows that (1) gramicidin is functional on an automated platform, (2) the fluidics system of the platform have sufficient flexibility to enable the switch between two extracellular ionic gradient states while applying/removing ligand and (3) the chloride flux associated with transporter activity can be distinguished from that associated with channel activation. While some inherent limitations are challenging, such as the effectiveness of gramicidin, this successful proof-of-concept study demonstrates that it is now feasible to consider development of non-electrogenic transporter assays on automated electrophysiology platforms, which, if successful, could allow examination of a new target class with this technology.