The aim of the proposed research is to obtain information about the role of cyclic nucleotides and calcium ions in photoreceptor physiology. Little is known about the events by which the photoisomerization of rhodopsin in disk membranes induces a decrease in plasma membrane sodium conductance. It is thought that light induces a change in concentration of an intracellular transmitter substance near the site of photon absorption which diffuses to the plasma membrane and modulates the ionic conductance channels. Calcium ions and cyclic nucleotides have been proposed as internal transmitters in vertebrate photoreceptors. I propose to investigate the role of cGMP and Ca++ in excitation and adaptation by modifying the levels of cGMP and Ca++ in the voltage-clamped, isolated vertebrate photoreceptor. This preparation will eliminate the ambiguities due to electrical coupling and voltage-dependent conductance changes.
The specific aims of the proposed research are: 1) To determine whether experimentally-induced (by Ca++, cyclic nucleotide or H+ manipulation) voltage changes derive from the same ionic mechanisms which are responsible for the light-induced physiological change in rod membrane voltage. 2) To determine if the light-mediated decline in cGMP levels does indeed elicit the changes in membrane voltage and current observed during the receptor potential. 3) To evaluate the possibility that either lowered cGMP levels in a dark-adapted rod, or raised cGMP levels in a light-adapted rod, changes the state of adaptation. 4) To investigate the effects of cyclic nucleotides upon the physiological light response in the vertebrate cone. These experiments will provide new information about the visual transduction process which should have real significance for understanding transduction in other sense receptors and could also provide important perspectives which could have general application in neurobiology and neurochemistry. Pathologic accumulations of one of the putative transmitters (cGMP) is a feature in retinal dystrophy, which results in photoreceptor degeneration. It is hoped that insights into the molecular mechanisms of transduction may provide clues about the pathogenic mechanisms in these dystrophies, and more detailed information about the normal regulation of sodium channels.
| Waloga, G; Anderson, R E (1985) Effects of inositol-1,4,5-trisphosphate injections into salamander rods. Biochem Biophys Res Commun 126:59-62 |
