Extracellular ATP4- permeabilizes thymocytes not only to cations but also to low-molecular-weight solutes

Extracellular ATP increases the free cytosolic calcium concentration ([Ca2+]i) of thymocytes by changing the membrane permeability to divalent cations: (1) no [Ca2+]i elevation is observed in the absence of extracellular calcium and (2) ATP also promotes Mn2+ entry into thymocytes, as shown by a stimulated quench of the fluorescence of Quin2-loaded cells. Using 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5- hexatriene, a dye which usually does not pass through membranes, we showed that ATP permeabilizes thymocyte membranes not only to cations but also to low-molecular-weight solutes. The ATP effect is dose-dependent, specific and reversible; ATP4- appears to be the active species and probably acts through specific receptor(s). Both medullary and cortical thymocytes respond to ATP whereas splenocytes do not; this shows that the ATP effect is restricted to certain populations of lymphocytes. The thymoma-derived cell line, EL-4, the permeability of which is also sensitive to ATP, could provide a useful model for studying the putative ATP4- receptor(s) of thymocytes.