Extracellular protons modulate the Ca2+ block of a Ca(2+)-blockable monovalent cation channel in chick embryo

Some epithelial nonselective cation channels although in an open conformation are impermeable because they are blocked by extracellular Ca2+ ions. Such a channel is present in the apical membrane of the ectodermal cells of the chick gastrula. This single-channel study shows that protonation of a site located inside the pore of this embryonic channel reduces the Ca2+ block thus allowing Na+ to pass. The apparent pK for Ca2+ at -50 mV shifts from 5.7 at pH 7.4 to 3.5 at pH 4.5. Unexpectedly, the change in Ca2+ affinity does not originate from a destabilization of the binding but comes from a large reduction of the association rate.