FMRFAMIDE PRODUCES BIPHASIC MODULATION OF THE LFS MOTOR-NEURONS IN THE NEURAL CIRCUIT OF THE SIPHON WITHDRAWAL REFLEX OF APLYSIA BY ACTIVATING NA+ AND K+ CURRENTS

The molluscan neuropeptide FMRFamide has an inhibitor effect on transm itter release from the presynaptic sensory neurons in the neural circu it for the siphon withdrawal reflex We have explored whether FMRFamide also acts postsynaptically in motor neurons in this circuit, focusing on the LFS motor neurons. FMRFamide typically produces a biphasic res ponse in LFS neurons: a fast excitatory response followed by a prolong ed inhibitory response. We have analyzed these postsynaptic actions an d compared them with the mechanism of FMRFamide's inhibition of the pr esynaptic sensory neurons. The transient excitatory effect of FMRFamid e, which desensitizes rapidly, is due to activation of a TTX-insensiti ve, Na+-dependent inward current. The late hyperpolarizing phase of th e FMRFamide response results from activation of at least two K+ curren ts. One component of the hyperpolarizing response is active at rest an d at more hyperpolarized membrane potentials, and is blocked by 5 mm 4 -aminopyridine, suggesting that it differs from the previously describ ed FMRFamide-modulated K+ currents in the presynaptic sensory neurons. In addition, FMRFamide increases a 4-aminopyridine-insensitive K+ cur rent. Presynaptically, FMRFamide increases K+ conductance, acting via release of arachidonic acid. In the LFS motor neurons, application of arachidonic acid mimicked the prolonged, hyperpolarizing phase of the FMRFamide response; 4-bromophenacyl bromide, an inhibitor of phospholi pase A2, selectively blocked this component of the FMRFamide response. Thus, FMRFamide may act in parallel pre- and postsynaptically to inhi bit the output of the siphon withdrawal reflex circuit, producing this inhibitory effect via the same second messenger in the sensory neuron s and motor neurons, though a number of the K + currents modulated in these two types of neurons are different.