A cation non-selective channel induced by extracellular ATP in macrophages and phagocytic cells of the thymic reticulum

AbstractExtracellular ATP4− can bind to P2Z purinergic receptors inducing depolarization and cytoplasmic membrane permeabilization to small molecular weight solutes in macrophages, thymocytes, mast cells, phagocytic cells of the thymic reticulum and other cell types. An ATP4−-induced cation current has been described in whole-cell records of some of these cells but it is currently not clear whether these currents and the phenomenon of membrane permeabilization are a consequence of only one type of P2Z- associated channel/pore or two different phenomena triggered by one or more receptors. Here we use the outside-out patch-clamp technique to describe a single channel associated with this cation current in two murine phagocytic cells: intraperitoneal macrophages and phagocytic cells of the thymic reticulum. Multi channel currents could be readily observed in 77% of the outside-out patches of macrophages. Single channels of 7.8 pS could usually be resolved only in tail currents. Reversal potential measurements and ion replacement experiments indicated a lack of cation selectivity, similarly to what has already been described for the ATP4−-induced whole-cell inward current. No large-conductance channels that could explain the permeabilization to small molecular weight solutes was observed under our experimental conditions. A single channel of approx. 5 pS was also observed in phagocytic cells of the thymic reticulum under similar conditions. We conclude that the channel here described is the main carrier of cation current usually associated with the binding of ATP4− to P2Z receptors in whole-cell and outside-out patch-clamp experiments