Inhibition by cytoplasmic nucleotides of a new cation channel in freshly isolated human and rat type II pneumocytes

Here we report a 26- to 29-pS cation channel abundantly expressed in freshly isolated and primary cultured type II cells from rat or healthy human lungs. The channel was never spontaneously active in cell-attached patches but could be activated by cell permeabilization with beta-escin. Excised patch-clamp experiments revealed activation by Ca2+ concentrations at the cytoplasmic side in the micromolar range. High concentrations of amiloride (>10 muM) at the extracellular side did not inhibit. The channel was equally permeable for K+ and Na+ but was essentially impermeable for Cl-, Ca2+, and Mg2+. It was blocked by adenosine nucleotides (cytoplasmic side) with the following order of potency: AMPapproximate toADP (EC(50)less than or equal to10 muM)>ATPmuch greater thanadenosinemuch greater thancyclic AMP. The blocking effect of ATP was reproduced by its nonhydrolyzable analogs AMPPNP or ATP-gamma-S. GTP did not inhibit. Cd2+ blocked the channel with an EC(50)approximate to55.5 nM. We conclude that type II cells express a Ca2+-dependent, nucleotide-inhibited, nonselective, and Ca2+-impermeable cation channel (NSCCa/AMP) with tonically suppressed activity. RT-PCR confirmed expression of TRPM4b, a channel with functional characteristics almost identical with NSCCa/AMP. Potential physiological roles are discussed.