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Sci Rep. 2018 Jun 4;8(1):8536. doi: 10.1038/s41598-018-26868-6.

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

Author information

1
Clinic for Anesthesiology, University Medical Center, Göttingen, Germany.
2
Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.
3
Department of Biochemistry, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, 31096, Israel.
4
Clinic for Anesthesiology, University Medical Center, Göttingen, Germany. shuelsm2@uni-goettingen.de.
5
Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany. shuelsm2@uni-goettingen.de.

Abstract

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.

PMID:
29867218
PMCID:
PMC5986860
DOI:
10.1038/s41598-018-26868-6
[Indexed for MEDLINE]
Free PMC Article

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