Facilitation of the responses to injections of inositol 1,4,5-trisphosphate analogs in Limulus ventral photoreceptors.

Injection of inositol 1,4,5-trisphosphate and its metabolically resistant analogs InsP3S3 and L-chiro-2,3,5-InsP3 into the ventral photoreceptors of Limulus results in the release of calcium from internal stores and in a current flow into the cells. We show here that the dependence of the current response on the amount of analog injected is supralinear. The injections also facilitate the responses to subsequent injections. We analyze the kinetics of the responses either by very slow application of the analogs directly into the lobe that is sensitive to InsP3 and light or by delivering a pulse into the nonsensitive lobe of the cell, in both cases creating a ramp of rising concentration in the sensitive region. Typically, a long latent period was followed by a strong brief inward current. The ratio between the latency and the duration of the response, defined as twice the time from half-amplitude to the peak of the response, reaches values greater than 10. Our analysis shows that this value cannot be attained within realistic models whose only nonlinearity is the cooperative binding of the ligand to its receptor. The observed ratio, however, can be achieved with a positive feedback model. Treatments that lead to partial depletion of calcium stores reversibly increase the latency of the response. We conclude that the mechanisms of the response of Limulus ventral eye to the metabolically resistant analogs of InsP3 probably involves a positive feedback mechanism and that the carrier of the feedback is likely to be Ca2+.