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© The Rockefeller University Press, 0022-1295/1999//35/ $5.00
Journal of General Physiology, Volume 113, Number 1, 1999

Article

Blockade of a Retinal cGMP-gated Channel by Polyamines

Zhe Lu* and Long Ding{ddagger}

From the * Department of Physiology and {ddagger} Neuroscience Graduate Group, University of Pennsylvania, Philadelphia, Pennsylvania 19104

The cyclic nucleotide–gated (CNG) channel in retinal rods converts the light-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 low noise, which enables rods to detect light with extremely high sensitivity. Here, we report that three polyamines (putrescine, spermidine, and spermine), which exist in both the intracellular and extracellular media, also effectively block the CNG channel from both sides of the membrane. Among them, spermine has the greatest potency. Extracellular spermine blocks the channel 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, K1/2 of the CNG channel for extracellular spermine is 3 µM, which is 100–1,000-fold higher affinity than that of the NMDA receptor-channel for extracellular spermine. Blockade of the CNG channel by polyamines may play an important role in suppressing noise in the signal transduction system in rods.

Key Words: cyclic nucleotide–gated channel • ion permeation • putrescine • spermidine • spermine

Address correspondence to Dr. Zhe Lu, University of Pennsylvania, Department of Physiology, D302A Richards Building, 3700 Hamilton Walk, Philadelphia, PA 19104-6085. Fax: 215-573-5851; E-mail: zhelu{at}mail.med.upenn.edu

Abbreviations: CNG, cyclic nucleotide–gated; I–V, current–voltage


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