Blockade of a retinal cGMP-gated channel by polyamines

The cyclic nucleotide-gated (CNG) channel in retinal rods converts the ligh t-regulated intracellular cGMP concentration to various levels of membrane potential. Blockade of the channel by cations such as Ca2+ and Mg2+ lowers its effective conductance. Consequently, the membrane potential has very lo w noise, which enables rods to detect light with extremely high sensitivity . Here, we report that three polyamines (putrescine, spermidine, and spermi ne), which exist in both the intracellular and extracellular media, also ef fectively block the CNG channel from both sides of the membrane. Among them , spermine has the greatest potency. Extracellular spermine blocks the chan nel as a permeant blocker, whereas intracellular spermine appears to block the channel in two conformations-one permeant, and the other non- (or much less) permeant. The membrane potential in rods is typically depolarized to approximately -40 mV in the dark. At this voltage, K-1/2 Of the CNG channel for extracellular spermine is 3 mu M, which is 100-1,000-fold higher affin ity than that of the NMDA receptor-channel for extracellular spermine. Bloc kade of the CNG channel by polyamines may play an important role in suppres sing noise in the signal transduction system in rods.