Molecular cloning and functional characterization of a new modulatory cyclic nucleotide-gated channel subunit from mouse retina

Cyclic nucleotide-gated (CNG) channels play a key role in olfactory and vis ual transduction. Native CNG channels are heteromeric complexes consisting of the principal alpha subunits (CNG1-3), which can form functional channel s by themselves, and the modulatory beta subunits (CNG4-5). The individual alpha and beta subunits that combine to form the CNG channels in rod photor eceptors (CNG1 + CNG4) and olfactory neurons (CNG2 + CNG4 + CNG5) have been characterized. In contrast, only an alpha subunit (CNG3) has been identifi ed so far in cone photoreceptors. Here we report the molecular cloning of a new CNG channel subunit (CNG6) from mouse retina. The cDNA of CNG6 encodes a peptide of 694 amino acids with a predicted molecular weight of 80 kDa. Among the CNG channel subunits, CNG6 has the highest overall similarity to the CNG4 beta subunit (47% sequence identity). CNG6 transcripts are present in a small subset of retinal photoreceptor cells and also in testis. Heter ologous expression of CNG6 in human embryonic kidney 293 cells did not lead to detectable currents. However, when coexpressed with the cone photorecep tor alpha subunit, CNG6 induced a flickering channel gating, weakened the o utward rectification in the presence of extracellular Ca2+, increased the s ensitivity for L-cis diltiazem, and enhanced the cAMP efficacy of the chann el. Taken together, the data indicate that CNG6 represents a new CNG channe l beta subunit that may associate with the CNG3 alpha subunit to form the n ative cone channel.