Molecular and pharmacological analysis of cyclic nucleotide-gated channel function in the central nervous system.

Most functional studies of cyclic nucleotide-gated (CNG) channels have been confined to photoreceptors and olfactory epithelium, in which CNG channels are abundant and easy to study. The widespread distribution of CNG channels in tissues throughout the body has only recently been recognized and the functions of this channel family in many of these tissues remain largely unknown. The molecular biological and pharmacological properties of the CNG channel family are summarized in order to put in context studies aimed at probing CNG channel functions in these tissues using pharmacological and genetic methods. Compounds have now been identified that are useful in distinguishing CNG channel activated pathways from cAMP/cGMP dependent-protein kinases or other pathways. The ways in which these interact with CNG channels are understood and this knowledge is leading to the identification of more potent and more specific CNG channel subtype-specific agonists or antagonists. Recent molecular and genetic analyses have identified novel roles of CNG channels in neuronal development and plasticity in both invertebrates and vertebrates. Targeting CNG channels via specific drugs and genetic manipulation (such as knockout mice) will permit better understanding of the role of CNG channels in both basic and higher orders of brain function.