PbCl2-induced hyperpolarization of rat thymocytes: involvement of charybdotoxin-sensitive K+ channels.

The effect of PbCl2 on membrane potential and intracellular divalent metal cation concentrations of rat thymocytes was examined by flow cytometry. PbCl2 at concentrations of 0.3 μM or higher (up to 10 μM) produced persistent, dose-dependent hyperpolarization (decrease in the intensity of di-BA-C4 fluorescence). Removal of external Ca2+ did not significantly affect the PbCl2-induced hyperpolarization. Charybdotoxin, a specific antagonist of Ca2+-dependent K+ conductance, greatly attenuated the PbCl2-induced hyperpolarization. PbCl2 increased the intensity of fluo-3 fluorescence under both normal Ca2+ and nominally Ca2+-free conditions. These results suggest that Pb2+ enters thymocytes, causing an increase in fluo-3 fluorescence, and activates Ca2+-dependent K+ channels, resulting in hyperpolarization. The persistent activation of K+ channels by Pb2+, leading to persistent hyperpolarization, may be one mechanism whereby Pb2+ alters immune function, as membrane potential changes influence physiological functions of lymphocytes. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 321–326, 2003.