Increased Anion Permeability During Volume Regulation in Human Lymphocytes

Peripheral blood lymphocytes (p.b.ls) readjust their volumes after swelling in hypotonic media. An essential component of the regulatory response is an increase in K$^+$ and Cl$^-$ permeability. No evidence was found for a tightly coupled co-transport of K$^+$ and Cl$^-$. The flux of either ion proceeds normally in the virtual absence of the transported counterion. Furthermore, alterations in membrane potential recorded during the phase of volume readjustment can be qualitatively accounted for by an increase in Cl$^-$ conductance. In tonsillar lymphocytes, a failure of the K$^+$-permeation path to respond to swelling leads to deficient volume recovery, but Cl$^-$ permeability is nevertheless increased upon swelling. This further suggests that K$^+$ and Cl$^-$ are transported during volume regulation through independent pathways. Cytoplasmic free Ca$^{2+}$ appears to be involved in regulatory volume decrease. K$^+$ and Cl$^-$ fluxes similar to those elicited by swelling can also be produced by A23187 plus Ca$^{2+}$. Moreover, swelling and shrinking can be induced in isotonic K$^+$-rich and K$^+$-free media, respectively, by the Ca$^{2+}$ ionophore. The ion flux and volume changes produced by either swelling or internal Ca$^{2+}$ can be inhibited by similar concentrations of quinine and phenothiazines. The inhibitory activity of the latter drugs, which are powerful antagonists of calmodulin, suggests the participation of this Ca$^{2+}$-regulator protein in volume regulation.