Regulation and Rapid Inactivation of the Light Induced cGMP Phosphodiesterase Activity in Vertebrate Retinal Rods

Abstract

The rhodopsin-transducin-cGMP phosphodiesterase cascade triggered by light in visual cells has become an archetype for the now ubiquitous G-protein mediated transduction processes (Stryer 1986, Deterre and Chabre 1989). Within a few hundred milliseconds of the photoisomerization of one rhodopsin in a rod cell, the cascade developps very rapidly and can induce the hydrolysis of hundred thousands of cGMP molecules. These fast kinetics are made possible first by the great mobility of rhodopsins and transducins, respectively in and on the rod disc membrane. The high gain is accounted for by the large number of transducins than can interact in rapid sequence with a single photoexcited rhodopsin. The activated TαGTP subunits of transducins are released in the quasi-two dimensionnai interdiscal space, in which they reach locally a very high concentration (~ 500 μM). They diffuse rapidly in the narrow cytoplasmic cleft and soon interact with the PDE bound onto the two limiting disc membrane surfaces. This interaction results in the derepression of the extremely rapid, cGMP specific, hydrolytic activity of a few hundred PDE molecules, hence inducing a rapid decrease of the cGMP concentration. The drop in cGMP concentration propagates from the interdiscal space to the cytoplasmic region beneath the outer cell membrane, at the level of the illuminated disc.