Calculations of K+, Na+, and Cl– Fluxes across Cell Membrane with Na+/K+ Pump, NKCC, NC Cotransport and Ionic Channels with Non Goldman Rectification in K+ Channels: Normal and Apoptotic Cells1

The balance of K+, Na+, and Cl– fluxes across the cell membrane with the Na+/K+ pump, ion channels, and Na+K+2Cl– (NKCC) and Na+–Cl– (NC) cotransport was calculated to determine the mech anism of cell shrinkage in apoptosis. It is shown that all unidirectional K+, Na+, and Cl– fluxes; the ion chan nel permeability; and the membrane potential can be found using the principle of the flux balance if the fol lowing experimental data are known: K+, Na+, and Cl– concentrations in cell water; total Cl– flux; total K+ influx; and the ouabain inhibited pump component of the Rb+(K+) influx. The change in different ionic pathways during apoptosis was estimated by calculations based on the data reported in the preceded paper (Yurinskaya et al., 2010). It is found that cell shrinkage and the shift in ion balance in U937 cells induced to apoptosis with 1 μM staurosporine occur due to the coupling of reduced pump activity with a decrease in the integral permeability of Na+ channels, whereas K+ and Cl– channel permeability remains almost unchanged. Calculations show that only a small part of the total fluxes of K+, Na+, and Cl– account for the fluxes medi ated by NKCC and NC cotransporters. Despite the importance of cotransport fluxes for maintaining the nonequilibrium steady state distribution of Cl–, they cannot play a significant role in apoptotic cell shrinkage because of their minority and cannot be revealed by inhibitors.