Cyclic nucleotide-gated (CNG) channels have been well characterized in the sensory receptors of vision and olfaction, but their characteristics in other tissues remain largely unknown. Here, we report characterization of a novel brain-specific CNG channel from zebrafish. Unique among CNG channels, the transcript is expressed mainly in the brain. When expressed in Xenopus oocytes, the channel's electrophysiological properties are distinct compared to CNG channels from either rods (CNGA1), olfactory receptors (CNGA2), or cones (CNGA3). The channel is less sensitive to cAMP than cGMP (K-1/2 of 280 and 7 mu M, respectively), with a maximum cAMP efficacy at least 80% of that with saturating levels of cGMP. The single-channel conductance of 58 pS is larger than most other CNG channels. Like other CNG channels the channel is relatively nonselective among monovalent cations. However, unlike other CNG channels, there was rundown of the macroscopic current within 30-100 min after patch excision. (c) 2006 Elsevier Inc. All rights reserved.