A neuronal role of the Alanine-Serine-Cysteine-1 transporter (SLC7A10, Asc-1) for glycine inhibitory transmission and respiratory pattern

• Published in: Scientific reports Vol. 8; no. 1; pp. 8536 - 8
• Main Authors: Mesuret, Guillaume, Khabbazzadeh, Sepideh, Bischoff, Anne M., Safory, Hazem, Wolosker, Herman, Hülsmann, Swen
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.06.2018; Nature Publishing Group
• Subjects: 14/35; 631/378/548/1964; 631/443/1784; 64/60; 9/74; Alanine; Brain stem; Cysteine; Experiments; Glycine; Humanities and Social Sciences; Isoleucine; multidisciplinary; Neurons; Phrenic nerve; Respiration; Science; Science (multidisciplinary); Serine; Synaptic transmission
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-26868-6

The Alanine-Serine-Cysteine-1 transporter (SLC7A10, Asc-1) has been shown to play a role in synaptic availability of glycine although the exact mechanism remains unclear. We used electrophysiological recordings and biochemical experiments to investigate the role of Asc-1 transporter in glycinergic transmission in the brainstem respiratory network. Using both the Asc-1 substrate and transportable inhibitor D-isoleucine (D-Ile), and the non-transportable Asc-1 blocker Lu AE00527 (Lu), we found that D-Ile reduces glycinergic transmission and increases glycine release via hetero-exchange, whereas Lu has no acute effect on glycinergic synaptic transmission. Furthermore, D-Ile increases the frequency and reduces amplitude of the phrenic nerve activity in the arterially-perfused working heart brainstem preparation. These results suggest a role of Asc-1 in modulating presynaptic glycine levels that can impact on the respiratory network.