Membrane potential changes associated with calcium signals in human lymphocytes and rat mast cells

Human lymphocytes and rat mast cells, two non-excitable cellular models, were used to investigate membrane potential changes accompanying Ca²⁺ signals. Cells were stimulated with agents known to induce both Ca²⁺ release from internal stores and influx of extracellular Ca²⁺, namely thapsigargin, ionomycin and compound 48/80. Thapsigargin and ionomycin were used to activate lymphocytes, while compound 48/80 was used to stimulate mast cells. Membrane potential changes and Ca²⁺ concentration were monitored with the fluorescent dyes bis-oxonol and fura-2, respectively. In lymphocytes, thapsigargin induced a hyperpolarization temporally correlated with the increase in intracellular Ca²⁺ concentration. This hyperpolarization is due to activation of a K⁺ conductance which consists of two phases, a first phase independent on external Ca²⁺ and a second one blocked in a Ca²⁺-free medium. Ionomycin induced a Ca²⁺-dependent depolarization attributed to a massive influx of external Ca²⁺. On the other hand, stimulation of mast cells with compound 48/80 produced a fast hyperpolarization and an increase in intracellular Ca²⁺ levels. Besides different time-courses, this hyperpolarization differs from that induced by thapsigargin in lymphocytes in two aspects., it is mainly due to a Cl^-- entry current and exit of K⁺ and it is completely inhibited in the absence of extracellular Ca²⁺. Compound 48/80-induced histamine release is not related to membrane potential changes.