Nitric oxide: an inhibitory retrograde modulator in the crustacean heart

The nervous system innervates most of the organs in the body, and controls and coordinates their activities. Effective coordination depends on accurate feedback from target organs. Recent studies have identified a target-based feedback mechanism that regulates a simple neural circuit, the cardiac ganglion-a network of nine neurons whose rhythmic bursts of action potentials drive the contractions of the crustacean heart. The feedback agent, nitric oxide (NO), is produced by the target organ (the heart), and acts on the neural circuit (the ganglion), thus serving as a retrograde, trans-synaptic signaling molecule. NO decreases the ganglionic burst rate, which has both negative chronotropic and negative inotropic effects on the heartbeat. This article will review the evidence identifying NO as an inhibitory modulator in the crustacean heart, and will present new data showing that these inhibitory effects are not mediated by cGMP, the canonical downstream agent mobilized by NO in many other systems. Rather, our data suggest that in the crustacean heart cGMP may play a secondary role in the process of adaptation that occurs in during prolonged exposures to NO.