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

✍ Scribed by Annarosa Arcangeli; Maria Riccarda Del Bene; Riccardo Poli; Letizia Ricupero; Massimo Olivotto

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: English
• Weight: 885 KB
• Volume: 139
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041390102

✦ Synopsis

This study deals with the modulation of the plasma membrane potential (A+,) of murine erythroleukemia (MEL) cells by cell-substratum or cell-cell contact. At& was determined by measuring the distribution of tetraphenylphosphonium (TPP+) across the plasma membrane; it appeared strongly, and inlersely, influenced by the two types of cell contacts. Contact with the culture surface produced a A+i, hyperpolarization directly proportional to average distance among the ideal centers of the cells on this surface (d) within the range 10-80 k m . A detailed mathematical analysis of the function A+,, = f(d) is presented, as well as experiments involving the use of ionophores (valinomycin and A231 87) 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 (Kc,) and some substratum-adherent factors that are shed by MEL cells and antagonize KCd 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 (a = 10 pn), produced a marked A+p 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.1 cation channels.

Direct cellular interactions with cells or extracellular substrata are fundamental in morphogenesis and embryonic development; in the adult they critically contribute to homeostatic processes, such as tissue and organ stability, immune responses, thrombosis, inflammation, and wound healing (Yamada, 1983; Mc-Clay and Ettensohn, 1987).

Despite their great variability, these interactions elicit stimuli on the plasma membrane that are apparently converted into cell responses by a restricted number of signal transducing systems to the nucleus (Berridge, 1985). In this way, the one-dimensional genome can specify and modulate a three-dimensional organism (Edelman, 1985), so that disturbed tissue topography underlies tumor development (Rubin, 1985), and alterations of cell-cell or cell-substrata interactions emerge as essential features of the invasive cancer phenotype (Coman, 1944; Greenberg et al., 1984; Alitalo and Vaheri, 1982).

Numerous experimental models are now available to study the biological effects of cell adhesion, i.e., the formation of stable molecular (receptor-ligand) binding of cells to one another or to extracellular materials, accompanied by substantial changes in cytoskeleton assembly (Grinnell, 1978;Edelman, 1986;Ekblom et al., 1986). No models exist, however, for assessing what effects may be generated by cell-cell and cell-substrata interactions before, or without, the onset of a stable adhesion. These interactions, hereafter designated as "contacts," involve nonspecific (e.g., electrostatic) properties of cell surfaces and substrata (Baier et al., 1968; Grinnell, 19781, as well as specific chemical mechanisms that do not necessarily produce a stabilized binding (McClay and Ettensohn, 1987). The demonstration that this contact can generate cellular signals would be important for the following two reasons: 1)