Mutual contact of murine erythroleukemia cells activates depolarizing cation channels, whereas contact with extracellular substrata activates hyperpolarizing Ca2+-dependent K+ channels

This study deals with the modulation of the plasma membrane potential (Δψp) of murine erythroleukemia (MEL) cells by cell‐substratum or cell‐cell contact. Δψp was determined by measuring the distribution of tetraphenylphosphonium (TPP+) across the plasma membrane; it appeared strongly, and inversely, influenced by the two types of cell contacts. Contact with the culture surface produced a Δψp hyperpolarization directly proportional to average distance among the ideal centers of the cells on this surface (d) within the range 10–80 μm. A detailed mathematical analysis of the function Δψp = f(d) is presented, as well as experiments involving the use of ionophores (valinomycin and A23187) and the conditioning of the culture surface. We concluded that the d‐dependent hyperpolarization (dDH) was the result of a complex interplay between the activating properties of substratum on Ca2+‐dependent K+ channels (KCa) and some substratum‐adherent factors that are shed by MEL cells and antagonize KCa activation (substratum‐attached cellular factors = SACF), By contrast, contact of the cells with each other, obtained by incubating MEL cells at d smaller than the average cell diameter (Φ = 10 μm), produced a marked Δψp depolarization. This intercellular contact‐dependent depolarization (ICDD) was unaffected by valinomycin; it was abolished by substituting Na+ in the external medium with a nondiffusible cation (choline), which shows that ICDD was sustained by Na+ influxes, probably mediated by stretch‐activated (s.a.) cation channels.