Cyclic nucleotide-regulated cation channels

Publisher Summary Cyclic nucleotides exert their physiological effects by binding to four major classes of cellular receptors: cAMP- and cGMP-dependent protein kinases, cyclic GMP-regulated phosphodiesterases, cAMP-binding guanine nucleotide exchange factors, and cyclic nucleotide-regulated cation channels. Two families of channels regulated by cyclic nucleotides are: the cyclic nucleotide-gated (CNG) channels and the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. CNG and HCN channels are members of the superfamily of voltage-gated cation channels. The two channel classes differ from each other with regard to their mode of activation. CNG channels are opened by direct binding of cAMP or cGMP. In contrast, HCN channels are principally operated by voltage. These channels open at hyperpolarized membrane potentials, and close on depolarization. HCN channels are also activated directly by cyclic nucleotides, which act by increasing the channel open probability. CNG channels are expressed in retinal photoreceptors and olfactory neurons, and play a key role in visual and olfactory signal transduction. CNG channels are also found at low density in some other cell types and tissues, such as brain, testis, and kidney. A cation current that is slowly activated by membrane hyperpolarization (termed Ih, If, or Iq) is found in a variety of excitable cells, including neurons, cardiac pacemaker cells, and photoreceptors. The best established function of Ih is to control heart rate and rhythm by acting as “pacemaker current” in the sinoatrial (SA) node.