Isoforms of the neuropeptide myosuppressin differentially modulate the cardiac neuromuscular system of the American lobster, Homarus americanus

Authors: OLEISKY, EMILY - Bowdoin College; STANHOPE, MEREDITH - Bowdoin College; Hull, Joe; DICKINSON, PATSY - Bowdoin College

Submitted to: Journal of Neurophysiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/18/2022
Publication Date: 3/1/2022
Citation: Oleisky, E.R., Stanhope, M.E., Hull, J.J., Dickinson, P.S. 2022. Isoforms of the neuropeptide myosuppressin differentially modulate the cardiac neuromuscular system of the American lobster, Homarus americanus. Journal of Neurophysiology. 127(3):702-713. https://doi.org/10.1152/jn.00338.2021.
DOI: https://doi.org/10.1152/jn.00338.2021

Interpretive Summary: The rhythmicity of lobster heart contractions is controlled by the nine neurons that comprise the cardiac ganglion (CG). The actions of a neuropeptide termed myosuppressin on the CG neurons can affect the frequency and strength of heart contractions. Modifications to neuropeptide structures, such as addition of an amide to the carboxyl terminus, glutamine-based cyclization at the amino terminus, disulfide bridging between cysteine amino acids, and/or the addition of a sulfate group to tyrosine amino acids, can expand the potential functional fates of the neuropeptide. How some of these modifications affect myosuppressin actions on the rhythmicity of the lobster were examined. Fully mature myosuppressin, which has an amide at the carboxyl terminus and glutamine-based cyclization at the amino terminus, and a non-cyclized myosuppressin had similar effects on the lobster heart. In contrast, the effects of a non-amidated but cyclized myosuppressin were reduced relative to the mature neuropeptide. Taken together, these data suggest that myosuppressin regulation of lobster heart contractions are dependent on the carboxyl amide rather than cyclization at the amino terminus. These findings highlight the role that neuropeptide modifications have on downstream activities.

Technical Abstract: Post-translational modifications (PTMs) diversify peptide structure and allow for greater flexibility within signaling networks. The cardiac neuromuscular system of the American lobster, Homarus americanus, consists of a central pattern generator, the cardiac ganglion (CG), and peripheral cardiac muscle. Together, these components produce flexible output in response to peptidergic modulation. Here, we examined the role of PTMs in determining the effects of a cardioactive neuropeptide, myosuppressin (pQDLDHVFLRFamide), on the whole heart, the neuromuscular junction/muscle, the isolated CG, and the neurons of the CG. Mature myosuppressin and non-cyclized myosuppressin (QDLDHVFLRFamide) elicited similar and significant changes in whole heart contraction amplitude and frequency, stimulated muscle contraction amplitude, and the bursting pattern of the intact and ligatured neurons of the ganglion. In the whole heart, non-amidated myosuppressin (pQDLDHVFLRFG) elicited only a small decrease in frequency and amplitude. In the absence of motor neuron input, non-amidated myosuppressin did not cause any significant changes in the amplitude of stimulated contractions. In the intact CG, non-amidated myosuppressin elicited a small but significant decrease in burst duration. Further analysis revealed a correlation between the extent of modulation elicited by non-amidated myosuppressin in the whole heart and the isolated, intact CG. When the neurons of the CG were physically decoupled, non-amidated myosuppressin elicited highly variable responses. Taken together, these data suggest that amidation, but not cyclization, is critical in enabling this peptide to exert its effects on the cardiac neuromuscular system.