Spatial Spread of Second Messenger Signals in Rod Photoreceptor Outer Setments

Activation of a G protein-coupled signal transduction cascade by an external stimulus triggers the generation of an intracellular signal that carried by a diffusible cytoplasmic messenger whose action depends on, among other things how far it spreads from its ite of production. To address questions about the spatial spread of second messenger signals focal current recording and imaging were used to measure the longitudinal spread of changes in cGMP and Cu produced by focal illumination of a functionally intact isolated rod outer segments (ROS) in whole cell voltage clamp. The light-evoked changes in both messengers decayed with distance from a site of steady focal activation with essentially identical length constants of ~ 3 microns. These results can be understood on the basis of a quantitative model of coupled diffusable messengers which is likely to have broad relevance in second messenger signaling pathways. Length constants for the spread of adaptational changes produced by steady local illumination were the same for the reduction of the initial gain, and sensitivity of the light response (2.9 and 3.3 microns, respectively) consistent with Ca being the adaptation signal that controls these parameters. The characteristic length, however, for the spread of adaptational changes in response kinetics (time-to-peak) was 5.3 microns, substantially longer than 3 microns, suggesting that a diffusable messenger other than Ca or cGMP controls this feature of the electrical response.