ATP-INDUCED AND UTP-INDUCED CURRENTS IN MACROPHAGES AND MACROPHAGE POLYKARYONS

We have investigated the currents induced by extracellular ATP (ATP(o) ), extracellular UTP, and other related compounds in macrophages. At p otentials of -20 to -60 mV, a typical response to ATP(o) puffs consist s of a fast-activating inward current followed by a transient outward current. The phenomenon lasts 5-20 s, but for sustained exposure to AT P the inward current persists for up to 10 min (our longest recording time). Both currents are inhibited by Mg2+, suggesting that the phenom enon is mediated by ATP4-. The outward current can be ascribed to a Ca 2+-dependent K+ conductance, and release of Ca2+ from intracellular st ores is at least in part responsible for this current. The inward curr ent has a reversal potential of approximately 0 mV, and it is nonspeci fic for monovalent cations. UTP, a nucleotide that induces an increase in the cytoplasmic concentration of free Ca2+ but does not permeabili ze macrophages, and ATP-gamma-S can also induce inward and outward cur rents similar to those described for ATP, but higher doses are require d. Adenosine and AMP produce no detectable effect, whereas ADP induces a small outward current. The implications of these results to the phe nomenon of ATP(o)-induced permeabilization of macrophage membranes to large molecules are discussed.