The excitation cascade of <it>Limulus </it>ventral photoreceptors: guanylate cyclase as the link between InsP₃-mediated Ca²⁺release and the opening of cGMP-gated channels

• Main Authors: Lisman John E, Richard Edwin A, Garger Alexander V
• Format: Article
• Language: English
• Published: BMC 2004-02-01
• Series: BMC Neuroscience
• Online Access: http://www.biomedcentral.com/1471-2202/5/7

<p>Abstract</p> <p>Background</p> <p>Early stages in the excitation cascade of <it>Limulus </it>photoreceptors are mediated by activation of G_qby rhodopsin, generation of inositol-1,4,5-trisphosphate by phospholipase-C and the release of Ca²⁺. At the end of the cascade, cGMP-gated channels open and generate the depolarizing receptor potential. A major unresolved issue is the intermediate process by which Ca²⁺elevation leads to channel opening.</p> <p>Results</p> <p>To explore the role of guanylate cyclase (GC) as a potential intermediate, we used the GC inhibitor guanosine 5'-tetraphosphate (GtetP). Its specificity <it>in vivo </it>was supported by its ability to reduce the depolarization produced by the phosphodiesterase inhibitor IBMX. To determine if GC acts subsequent to InsP₃production in the cascade, we examined the effect of intracellular injection of GtetP on the excitation caused by InsP₃injection. This form of excitation and the response to light were both greatly reduced by GtetP, and they recovered in parallel. Similarly, GtetP reduced the excitation caused by intracellular injection of Ca²⁺. In contrast, this GC inhibitor did not affect the excitation produced by injection of a cGMP analog.</p> <p>Conclusion</p> <p>We conclude that GC is downstream of InsP3-induced Ca2+ release and is the final enzymatic step of the excitation cascade. This is the first invertebrate rhabdomeric photoreceptor for which transduction can be traced from rhodopsin photoisomerization to ion channel opening.</p>