Systems, including apparatus and methods, for performing electrophysiological measurements on membranous samples, including living cells, isolated cell fragments (such as organelles), and/or artificial membranes (such as vesicles). The apparatus may include a high-throughput electrophysiological measurement system, and components thereof. This measurement system may include, among others, (1) a fluidics head for transferring samples and/or other compounds to a perforated measurement substrate, (2) a pressure-regulated plenum system for positioning samples on the substrate and subsequently forming a high-resistance electrical seal, (3) an activation system (such as a computer-controlled pulsed UV illumination module) for activating caged compounds, (4) an electronics head for applying and/or measuring voltage and/or current, and/or (5) a computer-controlled analysis system for collecting and/or analyzing data. The methods may include methods for performing high-throughput electrophysiological measurements on transporters and/or voltage or ligand-gated ion channels, sequentially and/or simultaneously.