Cation transport and growth regulation in neuroblastoma cells. Modulations of K⁺ transport and electrical membrane properties during the cell cycle

Abstract

Cation transport and membrane potential were studied during the cell cycle of neuroblastoma cells (clone Neuro-2A) to investigate the role of these parameters in growth regulation. The cells were synchronized by selective detachment of mitotic cells. The membrane potential and intracellular K+ activity were measured with conventional and K+-selective microelectrodes respectively. Both the membrane potential and K+ activity were high in mitosis, decreased to half maximal in G1 phase, and rose again during S phase. K+ efflux across the plasma membrane was studied with 42K+ as a radioactive tracer using a washing method for cells grown in monolayer and a continuous efflux method for mitotic cells in suspension. The intracellular K+ content and unidirectional K+ efflux rate obtained from these measurements showed modulations during the cell cycle similar to those of the membrane potential. Using equations of electrodiffusion theory the membrane permeabilities to K+ and Na+ were calculated. These permeabilities were high in mitosis, decreased rapidly in G1 phase and increased during S phase, followed by a transient decrease in G2 phase. A rapid increase was observed between G2 phase and the next mitosis. A similar pattern was obtained for the K+ conductance. K+ resistance changes during the cell cycle were similar to changes in the specific membrane resistance, measured by microelectrodes, except for the early cell cycle phases (mitosis and G1). These studies clearly demonstrate large modulations of the passive membrane permeability properties during the cell cycle. These modulations can be correlated with physicochemical membrane variations during the cell cycle, such as membrane fluidity and lateral mobility of lipids.

Effect of fatty acids on plasma membrane lipid dynamics and cation permeability in neuroblastoma cells

“…The temporal similarities in structural, dynamic and functional plasma membrane properties during the cell cycle of neuroblastoma cells [1][2][3][4][5][6] suggest a causal relationship between these properties. This relationship may possibly be based on variations in the plasma membrane composition during the cell cycle, due to cell cycle phase specific insertion of membrane components [14].…”

“…Membrane potentials (E m) were measured using conventional 3 M KCl-filled glass microelectrodes as described in detail previously [4].…”

“…0005-2736/82/0000-0000/$02.75 © 1982 Elsevier Biomedical Press decrease in the intracellular K ÷ activity [4]. These latter changes were found to be due to decreased Na ÷ and K ÷ permeability [4] and to decreased (Na ÷ + K ÷ )-ATPase activity [5,6].…”

“…These latter changes were found to be due to decreased Na ÷ and K ÷ permeability [4] and to decreased (Na ÷ + K ÷ )-ATPase activity [5,6].…”

“…Increases in cell surface area during the cell cycle of neuroblastoma cells occur principally just before and during mitosis [4], while a high rate of phospholipid synthesis is known to occur during Gi-phase in various other cell lines [7][8][9][10][11]. Furthermore, an excellent correlation has been demonstrated between lateral mobility of plasma membrane proteins and the optimal activity of the Na+,K+-pump during the cell cycle of neuroblastoma' cells [6].…”