MOLECULAR-CLONING AND EXPRESSION OF A MODULATORY SUBUNIT OF THE CYCLIC NUCLEOTIDE-GATED CATION CHANNEL

The cDNA of three variants of a cyclic nucleotidegated (CNG) channel m odulatory subunit (CNG4c-CNG4e) has been cloned, CNG4c, CNG4d, and CNG 4e differ slightly from each other within an amino-terminal sequence t hat was originally reported as part of the bovine retinal glutamic aci d-rich protein (GARP). The core region of CNG4 is homologous to the se cond subunit of the human rod photoreceptor channel (hRCNC2b), suggest ing that both proteins are alternatively spliced products of the bovin e and human homologue of the same gene, CNG4 transcripts are present i n retina, testis, kidney, heart, and brain. Expression of CNG4 in HEK2 93 cells did not lead to detectable currents, Coexpression of CNG4 wit h the principal subunit of the bovine testis CNG channel (CNG3) result ed in currents which differed in several aspects from that induced by CNG3 alone. The heterooligomeric CNG3/CNG4 and the homooligomeric CNG3 channels were modified by Ca2+-calmodulin and some calmodulin antagon ists, The results suggest that CNG4 forms functional heterooligomeric channels with CNG3 in vitro and probably also in intact tissues.