INHIBITORS OF CYCLIC-GMP PHOSPHODIESTERASE ALTER EXCITATION OF LIMULUS VENTRAL PHOTORECEPTORS IN CA2-DEPENDENT FASHION()

We have examined the hypothesis that Ca2+-dependent cyclic-GMP metabol ism may play a role in visual transduction in Limulos photoreceptors. Although phosphoinositide hydrolysis is central to phototransduction a nd phosphoinositide-dependent Ca2+-mobilization seems to be required f or transduction, the subsequent steps leading to ion channel gating (t he immediate cause of excitation) are not understood. Channels normall y opened in response to light can be opened in excised membrane patche s by cGMP but not by Ca2+, suggesting that cGMP acts as a channel liga nd in excitation. Using phosphodiesterase inhibitors, we investigated whether changes in cGMP metabolism could affect excitation. We report that zaprinast and IBMX increased the amplitudes and retarded the kine tics of physiological light responses. These effects were maximal for brightest stimuli. The effects were markedly enhanced in low Ca2+ cond itions. In contrast, excitation induced by direct IP3-injection and by direct Ca2+-injection were inhibited. These observations suggest that PI-induced excitation is dependent on cGMP metabolism in a Ca2+-depen dent manner, and they support the possibility that transduction involv es modification of cGMP metabolism by Ca2+-release resulting from phos phoinositide hydrolysis.