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

Abstract

This study deals with the modulation of the plasma membrane potential (delta psi p) of murine erythroleukemia (MEL) cells by cell-substratum or cell-cell contact. delta psi p 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 delta psi p hyperpolarization directly proportional to average distance among the ideal centers of the cells on this surface (d) within the range 10-80 microns. A detailed mathematical analysis of the function delta psi p = 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 (phi = 10 microns), produced a marked delta psi 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.) cation channels.

Potentiation of large conductance, Ca2+‐activated K+ (BK) channels by α5β1 integrin activation in arteriolar smooth muscle

“…Integrin-induced membrane hyperpolarization has been reported in other cell types (Arcangeli et al 1987(Arcangeli et al , 1989Hofmann et al 2001), but our results provide the first evidence that BK channel activation may be a key underlying mechanism in VSM. Arcangeli and colleagues first reported that FN-integrin interactions elicited hyperpolarization of murine erythroleukaemia cells (Arcangeli et al 1991), an effect presumably mediated by the activation of Ca 2+ -activated K + channels (Arcangeli et al 1987(Arcangeli et al , 1989. The same group has also shown that the activation of β1 integrins in neuroblastoma and haemopoietic tumour cells leads to sustained activation of hERG K + current (Hofmann et al 2001).…”

Targeting Ion Channels in Leukemias: A New Challenge for Treatment

“…These cells express Ca 2+ -dependent K + channels (BK Ca ) [24,25] that are transiently activated when differentiation is stimulated by cell adhesion onto fibronectin [26,27], or by application of classical inducers of erythroid differentiation [28]. Similar effects were observed in THP-1 human monocytic leukemia cells.…”

Molecular Proximity of Kv1.3 Voltage-gated Potassium Channels and β1-Integrins on the Plasma Membrane of Melanoma Cells

“…This is likely important since cell migration requires that integrins undergo numerous cycles of attachment and release. Integrin-toligand binding causes K ϩ channel activation (Arcangeli et al, 1989(Arcangeli et al, , 1991(Arcangeli et al, , 1996Becchetti et al, 1992), which may enhance Ca 2ϩ influx. For example, inhibition of K ϩ channels by TEA, 4-AP, and verapamil block Ca 2ϩ influx (Lepple-Wienhues et al, 1996;Yao and Kwan, 1999).…”

“…Hyperpolarization precedes a marked cell spreading in erythroleukemia cells (Arcangeli et al, 1991) and serves as a commitment signal to neuritogenesis in neuroblastoma cells (Arcangeli et al, 1993). Fibronectin binding promotes activation of Ca 2 ϩ -dependent K ϩ channels in murine erythroleukemia cells, HERG K ϩ channel currents in human preosteoclastic leukemia cells, and inwardly rectified K ϩ channels in neuroblastoma cells (Arcangeli et al, 1989(Arcangeli et al, , 1991Becchetti et al, 1992;Hofmann et al, 2001). Laminin also promotes inwardly rectifying K ϩ currents in neuroblastoma cells (Arcangeli et al, 1996).…”