Visual transduction begins with absorption of a photon by rhodopsin. Photoisomerization of the chromophore must somehow signal the photoreceptor synapse to alter its release of transmitter onto second-order neurons. This signal is produced by the cyclic GMP- activated ion channel. This ion channel then converts the signal of light into an electrical signal the brain can understand. This proposal focuses on cGMP-activated ion channels. I will examine structural rearrangements that occur in response to cGMP that are coupled to channel activation. I will use the following tools to study how this protein works; electrical recordings, to assay the flux of ions through the pore of the protein; molecular biology to alter the amino acid sequence of the protein and test specific models of its function; and protein chemistry to study interactions between domains of the proteins, between subunits, and between the channels and other cellular proteins. Through these experiments I expect to gain significant insight into how the cGMP-activated ion channels function during visual transduction.
