Role of extracellular Na and K in lymphocyte activation

The transmembrane electrical potential has been measured across human peripheral blood lymphocytes under culture conditions using equilibrium distributions of the lipophilic cation 3H-tetraphenylphosphonium (TPP). The TPP equilibrates to a steady-state level that gives calculated voltages of -80 mV for unstimulated lymphocytes. This value of the potential is constant during the first few hours of succinyl concanavalin A stimulation. When the transmembrane electrical potential is lowered by isotonic replacement of Na with K, this neither by itself stimulates proliferation nor does it inhibit mitogen-stimulated proliferation. Lymphocytes with similar membrane potentials, such as those incubated in normal-Na MEM and low-Na-mannitol MEM, exhibit drastically different proliferative responses to mitogen stimulation (Deutsch et al., 1981). These results show that isotonic replacement of K for Na prevents low Na inhibition of DNA synthesis and that at least during the first 2.5 hours of lymphocyte activation transmembrane electrical potential per se does not play a significant role in the activation process.