The effect of phosphodiesterase inhibitors on the electrical activity of toad rods

The membrane potential of toad rods was recorded during addition of small amounts of phosphodiesterase inhibitors to the extracellular medium. Separate application of 3-isobutyl-1-methylxanthine (IBMX), caffeine, theophylline, papaverine and RO 20-1724 slowed down the time course of rod photo-response to dim flashes of light. These changes were associated with a two to six-fold increase in the amplitude of photoresponse. The effects on kinetics may be described simply by an expansion of the photoresponse time scale. When the drug concentration was raised above a certain level, the rods showed supralinear behaviour whereby doubling of the intensity of a dim flash could increase the response more than two-fold. Under similar conditions rods also showed light sensitization whereby responses to dim flashes were enhanced in the presence of dim backgrounds. Taking the drug concentration that induced a two-fold increase in the time-to-peak, IBMX was found the most effective compound, followed by papaverine, RO 20-1724, theophylline and caffeine with relative effectivities 1, 1/2, 1/7, 1/40 and 1/100. Sensitivity, kinetics and supralinear behaviour may be restored to normal by steady background illumination while still in the presence of IBMX. However the intensity of the steady light, needed to restore the sensitivity to control levels, is not sufficient to accelerate the kinetics back to control values. In the presence of 50 microM-IBMX a dim steady background of light enhanced the response to dim flashes. When the intensity of the light background was increased rods were desensitized and the supralinear behaviour disappeared. The antagonism between the effects of IBMX and the effects of background illumination on the kinetics of photoresponse suggests that phosphodiesterase activity controls the time course of light response in vertebrate rods.