Extracellular proton alters the divalent cation binding affinity in a cyclic nucleotide-gated channel pore

Extracellular protons in the range of 10(-9) to 10(-5) M effectively suppressed Na+ current (K(1/2) = 10(-6.1)) through the bovine retinal guanosine 3',5'-cyclic mononucleotide-gated ion channel expressed in Xenopus oocytes. The reduction of channel current was mediated by a single glutamate residue (Glu363) within the pore-forming region of the channel, also involved in extracellular divalent cation binding. Increasing the concentration of extracellular proton decreased the binding affinity of the extracellular divalent cation (e.g. Sr2+) and the large difference of binding affinity previously observed between the wild-type and E363D mutant channel disappeared. These results indicate that the permeation characteristics of cyclic nucleotide-gated ion channel can be altered by extracellular pH through a single acidic residue in the channel conduction pathway.