cAMP, Ca²⁺, pH_i, and NO Regulate H-like Cation Channels That Underlie Feeding and Locomotion in the Predatory Sea Slug Pleurobranchaea californica

Abstract

A systems approach to regulation of neuronal excitation in the mollusc Pleurobranchaea has described novel interactions of cyclic AMP-gated cation current (I), Ca, pH, and NO. I appears in many neurons of feeding and locomotor neuronal networks. It is likely one of the family of hyperpolarization-activated, cyclic-nucleotide-gated currents (h-current) of vertebrate and invertebrate pacemaker networks. There are two isoforms. Ca regulates both voltage dependence and depolarization-sensitive inactivation in both isoforms. The Type 1 I of the feeding network is enhanced by intracellular acidification. A direct dependence of I on cAMP allows the current to be used as a reporter on cAMP concentrations in the cell, and from there to the intrinsic activities of the synthetic adenyl cyclase and the degradative phosphodiesterase. Type 2 I of the locomotor system is activated by serotonergic inputs, while Type 1 of the feeding network is thought to be regulated peptidergically. NO synthase activity is high in the CNS, where it differs from standard neuronal NO synthase in not being Ca sensitive. NO acidifies pH, potentiating Type 1, and may act to open proton channels. A cGMP pathway does not mediate NO effects as in other systems. Rather, nitrosylation likely mediates its actions. An integrated model of the action of cAMP, Ca, pH, and NO in the feeding network postulates that NO regulates proton conductance to cause neuronal excitation in the cell body on the one hand, and relief of activity-induced hyperacidification in fine dendritic processes on the other.

Comparative Analysis of Neuropeptides in Homologous Interneurons and Prohormone Annotation in Nudipleuran Sea Slugs

“…FMRFa was previously found in the VWCs ( Green et al, 2018 ) and was also found here within the SLB cells, which was surprising given that it inhibits feeding in other gastropods. In A. californica , the FMRFa peptide partially shifts feeding rhythms from ingestive to egestive and is released from sensory neurons to reduce accessory radula closer (ARC) muscle contractions ( Vilim et al, 2010 ).…”

“…In H. crassicornis we detected peptides from homologs to the FMRFa, SCP, LFRFamide (LFRFa), and feeding circuit activating peptides (FCAP) prohormones, and in M. leonina , peptides from homologs to the FMRFa, SCP, LFRFa, and myoinhibitory peptide (MIP)-related prohormones. The P. californica VWC has previously been shown to have peptides from the FMRFa and QNFLa [a homolog of the A. californica pedal peptide 4; ( Green et al, 2018 )] prohormones, and we found that it also contains peptides from the SCP prohormone. Thus, each species’ neuron expressed peptides from both the FMRFa and SCP prohormones, and both H. crassicornis and M. leonina expressed peptides from the LFRFa prohormone; however, each neuron also expressed peptides not seen in the others.…”

“…Five neurons were analyzed. In addition to the previously described peptides from the FMRFa and QNFLa prohormones ( Green et al, 2018 ), the VWC expressed both SCP A and SCP B .…”

“…In each species, application of MIP-related peptides drives contractions of the gut. Finally, the P. californica VWC contains peptides from the QNFLa prohormone that is a homolog to the A. californica pedal peptide 4 prohormone ( Green et al, 2018 ). Pedal peptide 4 has not been investigated physiologically, but in Biomphalaria glabrata was observed to be less abundant 12 days post-infection with the parasite Schistosoma ( Wang et al, 2017 ).…”