FRF PEPTIDES IN THE ARC NEUROMUSCULAR SYSTEM OF APLYSIA - PURIFICATION AND PHYSIOLOGICAL ACTIONS

1. One preparation that has proven to be advantageous for the study of neuromuscular modulation is the accessory radula closer (ARC) muscle of Aplysia californica and its motor neurons B15 and B16. In this stud y three members of a new peptide family have been purified from this w ell-characterized preparation. Because these peptides terminate in Phe -Arg-Phe-amide, we have named them FRF(A), FRF(B), and FRF(C). The FRF s are thus RFamide peptides and are related to the widely studied neur opeptide FMRFamide. 2. The FRFs are present in the ARC motor neuron B1 5 in small quantities. 3. When they are exogenously applied, the FRFs decrease the size of ARC muscle contractions elicited by stimulation o f either motor neuron B15 or B16. They appear to do this by a combinat ion of presynaptic and postsynaptic actions. 4. Presynaptically, the F RFs appear to act like the buccalins, another family of inhibitory ARC neuropeptides. Both families of peptides reduce the size of motor neu ron-elicited excitatory junction potentials (EJPs) presumably by decre asing presynaptic acetylcholine (ACh) release. 5. Postsynaptically, th e FRFs appear to depress contractions because they activate a characte ristic voltage-dependent, 4-amino-pyridine-sensitive K current in the ARC muscle. The same current is activated by a second class of ARC mod ulators: those that exert potentiating actions at low doses and inhibi tory actions at high doses, i.e., serotonin, the small cardioactive pe ptides (SCPs), and particularly the myomodulins. Receptors mediating a ctivation of the K current by the FRFs and the other modulators do, ho wever, appear to be different. 6. We hypothesize that the inhibitory a ctions of the FRFs prevent excessively large muscle contractions. If c ontraction size is limited, then contraction duration is also limited. This may allow faster and more energetically favorable switching betw een contractions of antagonistic muscles.