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.