Abstract
Cyclic nucleitides 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. Cyclic nucleotide-regulated cation channels are unique among these receptors because their activation is directly coupled to the influx of extracellular cations into the cytoplasm and to the depolarization of the plasma membrane. Two families of channels regulated by cyclic nucleotides have been identified, the cyclic nucleotide-gated (CNG) channels and the hyperpolarization-activated cyclic nucleotide-gated (HCN) 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. Apart from their voltage senstivity, HCN channels are also activated directly by cyclic nucleotides, which act by increasing the channel open probability.
Published Version
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