Volume regulation of human peripheral blood lymphocytes and stimulated proliferation of volume-adapted cells

Human peripheral blood lymphocytes exposed to hypotonic media (Ca/Mg-free, room temp.) first swell and then shrink. This shrinking response is characterized by a simple exponential with a half-time of 1.44±0.60 min (n=11) and its extent but not the half-time for a given hypotonicity is influenced by K⁺]₀. Using K-selective electrodes, we observe a change in K⁺]₀ when cells are diluted into hypotonic media. A half-time of 1.55±0.06 min (n=4) was obtained. A similar half-time was obtained by assay of total cell K using atomic absorption spectroscopy. At all osmolarities K⁺]_i was decreased from control values and was constant as K⁺]₀ was increased. Short-term incubation with ouabain (10⁻⁴ M) had no effect. Decreasing osmolarities progressively inhibited phytohemagglutinin-stimulated DNA synthesis, yet cell number and viability remained unaltered. Our evidence indicates that the volume response is mediated by a change in the passive permeability of the plasma membrane to K and/or to the accompanying anions, and that the consequently volume-adapted cells are growth-inhibited.