An ATP- and Ca2+-regulated Na+ channel in isolated intestinal epithelial cells.

When isolated intestinal epithelial cells are treated with 2 mM ATP, the unidirectional influx of Na+ to those cells increases from values near 50 to rates over 200 nmol . min-1 . mg protein-1. Calcium influx increases from 1 to 40 nmol . min-1 . mg protein-1. Within 2 min, the total cell Na+ increases two- to threefold, and total Ca+ increases about fivefold. The cells lose a major part of their capability for accumulating sugars during this interval. About 2 min after the time of ATP addition the normal permeability for Na+ and Ca2+ is restored, at which time the previously accumulated ions are rapidly extruded on a net basis until control levels are attained and the cells regain their usual sugar transport capability. The "repair" process requires Ca2+ in the incubation medium and is dependent on cellular uptake of Ca2+. Chlorpromazine (0.5 mM) blocks the Ca2+ entry route and the restoration of normal Na+ permeability. The Na+ entry route is selectively blocked by 4-acetamido-4'-isocyanostilbene-2,2'-disulfonic acid. The data show that ATP induces the influx of Na+ and Ca2+ by two different routes, which can be selectively inhibited. These ion flux routes may be involved in the events that allow intestinal tissue to convert from an absorptive state to a state in which net ion secretion occurs.