V_m-related extracellular potentials observed in red blood cells

Even in nonexcitable cells, the membrane potential V_m is fundamental to cell function, with roles from ion channel regulation, development, to cancer metastasis. V_m arises from transmembrane ion concentration gradients; standard models assume homogeneous extracellular and intracellular ion concentrations, and that V_m only exists across the cell membrane and has no significance beyond it. Using red blood cells, we show that this is incorrect, or at least incomplete; V_m is detectable beyond the cell surface, and modulating V_m produces quantifiable and consistent changes in extracellular potential. Evidence strongly suggests this is due to capacitive coupling between V_m and the electrical double layer, rather than molecular transporters. We show that modulating V_m changes the extracellular ion composition, mimicking the behaviour if voltage-gated ion channels in non-excitable channels. We also observed V_m-synchronised circadian rhythms in extracellular potential, with significant implications for cell–cell interactions and cardiovascular disease.