Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCB251

Poster Communications

The role of the alanine-Serine-Cysteine-1 transporter (SLC7A10, Asc-1) in glycinergic transmission in the pre-Bötzinger Complex

S. Hülsmann1, G. Mesuret1, A. Bischoff1, S. Khabbazzadeh1, H. Safory2, H. Wolosker2

1. Anaesthesiology, Universitätsmedizin Göttingen, Göttingen, Germany. 2. Technion-Israel Institute of Technology, Haifa, Israel.

Mice, which lack the Alanine-Serine-Cysteine-1 transporter (SLC7A10, Asc-1), show reduced glycinergic synaptic tranmission although the exact mechanism remains unclear. We conducted whole-cell voltage-clamp recordings and biochemical experiments to test the role of Asc-1 in glycinergic transmission in the pre-Bötzinger complex, the medullary core network that is critical for breathing. Using both, a transportable Asc-1 inhibitor (D-isoleucine) and the non-transportable antagonist (Lu AE00527), we found that D-isoleucine reduces glycinergic transmission and increases glycine release, whereas Lu AE00527 has no acute effect. Furthermore, D-isoleucine increases the frequency and reduces amplitude of the phrenic nerve activity in arterially perfused working heart brainstem preparation. Based on these results, we propose that Asc-1 is modulating the presynaptic levels of glycine and other small amino acids like D-serine using its hetero-exchange antiporter activity.

Where applicable, experiments conform with Society ethical requirements