Annotated protein:Neuronal acetylcholine receptor subunit alpha-5. Gene symbol: CHRNA5. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q2MKA5
antibody wiki:
SynGO gene info:SynGO data @ CHRNA5
Ontology domain:Biological Process
SynGO term:regulation of postsynaptic neurotransmitter receptor activity (GO:0098962)
Synapse type(s):cerebral cortex, acetylcholinergic
Annotated paper:Venkatesan S, et al. "Chrna5 is Essential for a Rapid and Protected Response to Optogenetic Release of Endogenous Acetylcholine in Prefrontal Cortex" J Neurosci. 2020 Sep 16;40(38):7255-7268 PMID:32817066
Figure(s):Figure 1,2 and 4
Annotation description:Figure 1E: Fast-rising phase of cholinergic responses in voltage clamp (-75 mV) in α5WT (top) and α5KO (bottom) were recorded and linear fit (green) to the first 50 ms of the response from the light onset.
Figure 1F: Bar graph represents the rising slope (in pA/s) of the current determined from the linear fit in α5WT and α5KO. α5KO mice show a significantly slower onset of cholinergic responses as compared to WT.
Figure 1G: Average current-clamp response of α5WT and α5KO neurons.
Figure 1H: Bar graph representing the rising slope (mV/s) of the depolarization determined from the linear fit in α5WT and α5KO show a significantly slower onset of cholinergic responses from α5KO as compared to WT.
Table1: Other electrophysiological properties between α5KO and α5WT were not significantly different.

In order to test if the delayed effect on the onset was caused by the α5 subunit, pan-muscarinic receptor blocker, atropine was used.
Figure 2F and H: Fast-rising phase of cholinergic responses in α5WT and α5KO was recorded and linear fit (green) to the first 50 ms of the response from light onset after the application of atropine. The bar graph represents the rising slope (pA/s) of the current determined from the linear fit showing that α5KO shows a significantly slower onset of cholinergic responses from α5KO as compared to WT in the presence of atropine.
Figure 2G-I: The time of peak current, as measured from the exponential fits to the responses was significantly slower in α5KO as compared to α5WT.
Figure 2J: α5KO neurons show a significantly greater decay time constant compared with α5WT neurons.

Figure 4A-C: Blocking acetylcholinesterase causes the optogenetic cholinergic responses to nearly double in the α5WT, but the increase is not significant in the α5KO. α5KO neurons show smaller cholinergic responses compared with α5WT neurons following cholinesterase block because they might be susceptible to greater desensitization in the prolonged presence of high acetylcholine levels at the synapse.
Figure 4D-G: The α5WT optogenetic cholinergic response is unchanged by the application of nicotine, whereas the α5KO optogenetic response is rapidly attenuated. While α5KO neurons exhibit 80% desensitization at the end of a 10 min exposure and a τdecay of 5.7 min, α5WT neurons show only 2.5% desensitization. Chrna5 is protective against desensitization by low agonist concentrations, and more resilient than non-alpha5-containing nicotinic receptors found in the α5KO at higher agonist concentrations.

Thus, Chrna5 is essential to protect prefrontal endogenous cholinergic signalling from desensitization induced either by high acetylcholine levels or acute exposure to nicotine.
Evidence tracking, Biological System:Intact tissue
Evidence tracking, Protein Targeting:Genetic transformation (eg; knockout, knockin, mutations)
Evidence tracking, Experiment Assay:Whole-cell patch clamp
Annotator(s):Dnyanada Sahasrabudhe (ORCID:0000-0003-2916-7616)
Guus Smit (ORCID:0000-0002-2286-1587)
Matthijs Verhage (ORCID:0000-0002-2514-0216)
Lab:Department of Functional Genomics, Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
Additional literature:Figure2: Darkfield photomicrographs show alpha5 mRNA expression in the developing cortex. @ PMID:15558717
SynGO annotation ID:4536
Dataset release (version):20231201
View annotation as GO-CAM model:Gene Ontology