REGULATION OF CATION-SELECTIVE CHANNELS IN LIVER-CELLS

In liver cells, cation-selective channels are permeable to Ca2+ and ha ve been postulated to represent a pathway for receptor-mediated Ca2+ i nflux. This study examines the mechanisms involved in the regulation o f these channels in a model liver cell Line. Using patch-clamp recordi ng techniques, it is shown that channel open probability is a saturabl e function of cytosolic [Ca2+], with half-maximal opening at 660 nM. B y contrast, channel opening is not affected by membrane voltage or cyt osolic pH. In intact cells, reduction of cytosolic [Cl-], a physiologi cal response to Ca2+-mobilizing hormones and cell swelling, is also as sociated with an increase in channel opening. Finally, channel opening is inhibited by intracellular ATP through a mechanism that does not i nvolve ATP hydrolysis. These findings suggest that opening of cation-s elective channels is coupled to the metabolic state of the cell and pr ovides a positive feedback mechanism for regulation of receptor-mediat ed Na+ and Ca2+ influx.