Measuring Absolute Membrane Potential Across Space and Time.

Membrane potential (V_mem) is a fundamental biophysical signal present in all cells. V_mem signals range in time from milliseconds to days, and they span lengths from microns to centimeters. V_mem affects many cellular processes, ranging from neurotransmitter release to cell cycle control to tissue patterning. However, existing tools are not suitable for V_mem quantification in many of these areas. In this review, we outline the diverse biology of V_mem, drafting a wish list of features for a V_mem sensing platform. We then use these guidelines to discuss electrode-based and optical platforms for interrogating V_mem. On the one hand, electrode-based strategies exhibit excellent quantification but are most effective in short-term, cellular recordings. On the other hand, optical strategies provide easier access to diverse samples but generally only detect relative changes in V_mem. By combining the respective strengths of these technologies, recent advances in optical quantification of absolute V_mem enable new inquiries into V_mem biology.