Potentiation of GABAA receptor-mediated Cl- current by urotensin peptides in identified Aplysia neurons

Abstract

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the vertebrate and invertebrate central nervous systems, including those of molluscs. The effects of extracellularly applied urotensin peptides (urotensin I (UI) and urotensin II (UII)) on the GABA-induced Cl- current recorded from identified neurons (R9 and R12) of Aplysia kurodai were investigated using voltage-clamp and pressure ejection techniques. Focal application of 100 nM UI and UII potentiated the GABA-induced Cl- current without affecting the resting membrane conductance and holding current. The increase was completely reversible. The GABA-induced Cl- current also was potentiated by bath-applied UI and UII (5-10 nM). The potentiating effects of UI and UII on the GABA-induced Cl- current were concentration-dependent and completely reversible. These results suggest that neurotensin peptides may decrease neuronal excitability by potentiating the GABA(A) receptor-mediated Cl- current in the neurons of mammalian and invertebrate central nervous systems.

International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, Urotensin II–Related Peptide, and Their Receptor: From Structure to Function

“…In contrast, UII-like sequences have not been detected in the sea lamprey (Petromyzon marinus; Decatur et al, 2013) and in nonvertebrate chordates, such as tunicates or amphioxus. The existence of a UII-like peptide was recently reported in the marine mollusc Aplysia californica (Romanova et al, 2012), and UII has been found to potentiate GABA A receptor-mediated chloride current in Aplysia neurons (Sawada and Ichinose, 1999), suggesting that UII is an ancient peptide that existed before the emergence of vertebrates. However, two observations cast doubt on this hypothesis: 1) the sequence of the Aplysia UII-like peptide is not located at the C terminus of its precursor, as for all other members of the UII/URP family; and 2) although several other protostomian species do possess an orthologous UII-like precursor gene, they are apparently devoid of UT-like gene (personal communication).…”

Urotensin‐II regulates intracellular calcium in dissociated rat spinal cord neurons

“…At the present time, information relative to the functional role of U-II in the nervous system is limited. The only study to date showed a potentiation of GABA effects in Aplysia neurons (Sawada and Ichinose 1999). In the present study, we investigated the effects of U-II on [Ca 2+ ] i homeostasis in rat spinal motoneurons and the underlying signal transduction mechanisms.…”