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| Hauptseite > Publikationsdatenbank > Subunit-specific photocontrol of glycine receptors by azobenzene-nitrazepam photoswitcher > print |
| Hauptseite > Publikationsdatenbank > Subunit-specific photocontrol of glycine receptors by azobenzene-nitrazepam photoswitcher > print |
| 001 | 889058 | ||
| 005 | 20240625095119.0 | ||
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| 100 | 1 | _ | |a Maleeva, Galyna |0 P:(DE-HGF)0 |b 0 |e Corresponding author |
| 245 | _ | _ | |a Subunit-specific photocontrol of glycine receptors by azobenzene-nitrazepam photoswitcher |
| 260 | _ | _ | |a Washington, DC |c 2021 |b Society for Neuroscience |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 520 | _ | _ | |a Photopharmacology is a unique approach that through a combination of photochemistry methods and advanced life science techniques allows the study and control of specific biological processes, ranging from intracellular pathways to brain circuits. Recently, a first photochromic channel blocker of anion-selective GABAA receptors, Azo-NZ1, has been described. In the present study using patch-clamp technique in heterologous system and in mice brain slices, site-directed mutagenesis and molecular modelling we provide evidence of the interaction of Azo-NZ1 with glycine receptors (GlyRs) and determine the molecular basis of this interaction. Glycinergic synaptic neurotransmission determines an important inhibitory drive in the vertebrate nervous system and plays a crucial role in the control of neuronal circuits in the spinal cord and brain stem. GlyRs are involved in locomotion, pain sensation, breathing and auditory function, as well as in the development of such disorders as hyperekplexia, epilepsy and autism. Here we demonstrate that Azo-NZ1 blocks in a UV dependent manner the activity of alpha2 GlyRs (GlyR2), while being barely active on alpha1 GlyRs (GlyR1). The site of Azo-NZ1 action is in the chloride-selective pore of GlyR at the 2’ position of transmembrane helix 2 and amino acids forming this site determine the difference in Azo-NZ1 blocking activity between GlyR2 and GlyR1. This subunit specific modulation is also shown on motoneurons of brainstem slices from neonatal mice that switch during development from expressing "foetal" GlyR2 to "adult" GlyR1 receptors. |
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