A novel hypertonicity-induced cation channel in primary cultures of human hepatocytes

In whole-cell recordings on primary cultures of human hepatocytes, we observe the hypertonic activation of a novel type of cation channel with a permeability ratio for Na+:Li+:K+:Cs+:NMDG+ of 1:1.2:1.3:1.2:0.6. With a PCa/PNa of 0.7 the channel is also clearly permeable to Ca++. Most likely, the channel is Cl− impermeable but its activity critically depends on the extracellular Cl− concentration (with the half maximal effect at 88 mmol/l). With a 64% inhibition by amiloride and a complete block by flufenamate and Gd3+ (at 100 μmol/l each), the channel may represent a molecular link between the amiloride-sensitive and insensitive channels reported so far.