Analysis of the monovalent ion fluxes in U937 cells under the balanced ion distribution: Recognition of ion transporters responsible for changes in cell ion and water balance during apoptosis

Abstract

Unidirectional (22)Na, Li(+) and Rb(+) fluxes and net fluxes of Na(+) and K(+) were measured in U937 human leukemic cells before and after induction of apoptosis by staurosporine (1 microM, 4 h) to answer the question which ion transporter(s) are responsible for changes in cell ion and water balance at apoptosis. The original version of the mathematical model of cell ion and water balance was used for analysis of the unidirectional ion fluxes under the balanced distribution of major monovalent ions across the cell membrane. The values of all major components of the Na(+) and K(+) efflux and influx, i.e. fluxes via the Na(+),K(+)-ATPase pump, Na(+) channels, K(+) channels, Na/Na exchanger and Na-Cl symport were determined. It is concluded that apoptotic cell shrinkage and changes in Na(+) and K(+) fluxes typical of apoptosis in U937 cells induced by staurosporine are caused by a complex decrease in the pump activity, Na-Cl symport and integral Na(+) channel permeability.

Computation of Pump-Leak Flux Balance in Animal Cells

“…This inverse problem is much harder than finding concentrations from known parameters, and we approach it by trial and error. In the case of U937 cells, [Na] i , [K] i , [Cl] i , cell water content per unit of A , the pump coefficient β and OSOR were measured as described previously [11,12,13,14,15]. These data proved sufficient to find a unique set of parameters corresponding to the balanced state for a model that includes the pump, Na + , K + , Cl - channels and a single type of cotransport.…”

“…Salts were of analytical grade and were from Reachem (Russia). The experimental methods used in this work have been described in detail earlier [11,12,13,14,15]. Briefly, intracellular K + , Na + and Rb + content was analyzed by flame emission spectrometry, Cl - content was measured using 36 Cl - isotope.…”

“…For our study we chose the proliferating human lymphoid U937 cell line, which better represents the typical animal cell owing to its faster metabolism and intermediate (-40÷-60 mV) MP. The monovalent ion flux balance in U937 cells has been comprehensively characterized in our laboratory [11,12,13,14]. In the present paper we have developed an improved computational model which, compared to the previous models, uses phenomenological parameters derived from the balanced state.…”

Features of coupled Na+, K+, 2Cl–-cotransport with erythrocyte β-adrenergic system in bronchial asthma

“…-вовлечен в регуляцию разнооб разных клеточных функций (через влияние на кле точный объем), включая пролиферацию, рост, программируемую гибель и некроз [11][12][13][14].…”

Pump and Channel K^+ (Rb^+) Fluxes in Apoptosis of Human Lymphoid Cell Line U937

“…It was reported that at least 14 species of K + channels are involved somehow in apoptosis of various cells [2]. However, calculation of the changes in ion and water balance caused by an increase in the integral permeability of K + channels showed that significant cell shrinkage in apoptosis due to increase in the permeability of the K + channels can occur only under specific conditions [14][15][16]. In addition, an increase in the integral permeability 188 of K + channels conventionally associated with the opening of channels should lead to hyperpolarization of apoptotic cells whereas depolarization was mostly observed [12,[17][18][19][20][21].…”