Certain ganglion cells in the mammalian retina are known to
express a cGMP-gated cation channel. We found that a cGMP-gated
current modulates spike responses of the ganglion cells in mammalian
retinal slice preparation. In such cells under current clamp, bath
application of the membrane-permeant cGMP analog (8-bromo-cGMP,
8-p-chlorophenylthio-cGMP) or a nitric oxide donor (sodium
nitroprusside, S-nitroso-N-acetyl-penicillamine) depolarized the membrane
potential by 5–15 mV, and reduced the amount of current needed
to evoke action potentials. Similar effects were observed when the
membrane potential was simply depolarized by steady current. The
responses to cGMP are unaffected by inhibitors of cGMP-dependent protein
kinase and Ca2+/calmodulin-dependent protein kinase. The
response to cGMP persisted in Ca2+-free bath solution with
Ca2+ buffers in the pipette. Under voltage clamp, cGMP
analogs did not affect the response kinetics of voltage-gated
currents. We conclude that cGMP modulates ganglion cell spiking
simply by depolarizing the membrane potential via the
inward current through the cGMP-gated channel. Modulation of
this channel via the long-range NO-synthase amacrine
cell may contribute to control of contrast gain by peripheral
mechanisms.