ATP- and UTP-induced currents in macrophages and macrophage polykaryons

Abstract

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