A cGMP-gated cation channel and phototransduction in depolarizing photoreceptors of the lizard parietal eye.

Photoreceptors of the lizard parietal eye, unlike rods and cones but like most invertebrate photoreceptors, respond to light under dark-adapted conditions with a depolarization. Using excised-patch recordings, we have nonetheless found a cGMP-gated, non-selective cation channel present at high density at the presumptive light-sensitive part (the outer segment) of these cells. This channel resembles the rod cGMP-gated channel in its activation characteristics, and by showing a relative non-selectivity among alkali monovalent cations, a high permeability to Ca2+, a high sensitivity to L-cis-diltiazem, as well as a negative modulation by Ca(2+)-calmodulin. This channel appears to mediate phototransduction by opening in the light to produce the depolarizing response.

An unusual cGMP pathway underlying depolarizing light response of the vertebrate parietal-eye photoreceptor.

All cellular signaling pathways currently known to elevate cGMP involve the activation of a guanylyl cyclase to synthesize cGMP. Here we describe an exception to this rule. In the vertebrate parietal eye, the photoreceptors depolarize to light under dark-adapted conditions, unlike rods and cones but like most invertebrate photoreceptors. We report that the signaling pathway for this response involves a rise in intracellular cGMP resulting from an inhibition of the phosphodiesterase that hydrolyzes cGMP. Furthermore, this phosphodiesterase is driven by an active G protein in darkness. These results indicate an antagonistic control of the phosphodiesterase by two G proteins, analogous to the Gs/Gi control of adenylyl cyclase. Our findings demonstrate an unusual phototransduction mechanism and at the same time indicate that signaling involving cyclic nucleotides is more elaborate than previously known.

A cGMP-gated cation channel in depolarizing photoreceptors of the lizard parietal eye.

Rods and cones of the two vertebrate lateral eyes hyperpolarize when illuminated, a response generated by a cyclic GMP cascade leading to cGMP hydrolysis and consequently the closure of cGMP-gated, non-selective cation channels that are open in darkness. Lizards and other lower vertebrates also have a parietal (third) eye, which contains ciliary photoreceptors that under dark-adapted conditions depolarize to light instead. Depolarizing light responses are characteristic of most invertebrate rhabdomeric photoreceptors, and are thought to involve a phosphoinositide signalling pathway (see, for example, refs 7-9). Surprisingly, we have found in excised membrane patches a cGMP-gated channel that is selectively present at high density on the outer segment (the presumptive light-sensitive part) of the parietal eye photoreceptor. Like the light-activated channel of the cell, it is non-selective among cations. Inositol trisphosphate (InsP3) had no effect on the same membrane patches. These findings suggest that the photoreceptors of the parietal eye, like rods and cones, use a cGMP cascade and not an InsP3-mediated pathway for phototransduction, but in this case light increases cGMP. A unifying principle of evolutionary significance emerges: that phototransductions in various ciliary photoreceptors, whether hyperpolarizing or depolarizing, uniformly use a cGMP cascade and a cGMP-gated channel to generate the light response, although there are rich variations in the details.