Cyclic Nucleotide-Gated Ion Channels

Structural basis of properties, mechanisms, and channelopathy of cyclic nucleotide-gated channels

“…Thus, vertebrate CNG channels conduct substantial inward Ca 2+ currents at physiological concentrations [ 4 ], which is important for proper phototransduction and olfactory transduction and their regulation by Ca 2+ [ 3–6 ]. Paradoxically, Ca 2+ (as well as Mg 2+ ) blocks monovalent cation currents with a wide ranging apparent affinity of 3–500 μM in different types of CNG channels [ 4 , 12 , 59–61 , 65 , 69–72 ]. Due to the dual action of Ca 2+ , the mean single-channel conductance of rod CNG channels is only ~0.1 pS under physiological conditions [ 12 ].…”

“…Paradoxically, Ca 2+ (as well as Mg 2+ ) blocks monovalent cation currents with a wide ranging apparent affinity of 3–500 μM in different types of CNG channels [ 4 , 12 , 59–61 , 65 , 69–72 ]. Due to the dual action of Ca 2+ , the mean single-channel conductance of rod CNG channels is only ~0.1 pS under physiological conditions [ 12 ]. This very low single-channel conductance gives rise to an excellent signal-to-noise ratio and aligns well with the ability of rod photoreceptors to detect a single photon [ 73 ].…”

“…Replacing R880 with glycine increases the single-channel conductance of CNGA1/CNGB1 by ~60% [ 33 ], indicating a critical role of the arginine gate in modulating ion conduction in heteromeric CNG channels. The arginine gate may contribute to the flickery single-channel gating of native rod and cone CNG channels and heterologously express CNGA/CNGB channels [ 4 , 12 ]. Consistent with this hypothesis, flickery gating behavior is much less pronounced in homomeric CNGA channels, where the arginine is replaced by glycine or serine ( Figure 2 ).…”

“…Vertebrate CNG channels can be blocked by membrane-permeable L- cis -diltiazem (DTZ) [ 4 , 12 , 55 , 82 , 83 ]. This block takes place from the cytoplasmic side and is voltage-dependent [ 4 , 83–85 ], indicative of a binding site in the pore.…”