Involvement of GABAA receptors containing α6 subtypes in antisecretory factor activity on rat cerebellar granule cells studied by two‐photon uncaging. (20th July 2022)

• Record Type: Journal Article
• Authors: Bazzurro, Virginia; Gatta, Elena; Angeli, Elena; Cupello, Aroldo; Lange, Stefan; Jennische, Eva; Robello, Mauro; Diaspro, Alberto
• Is Part Of: European journal of neuroscience. Volume 56:Number 5(2022)
• Page Start: 4505
• Page End: 4513
• Publication Date: 2022-07-20
• Subjects: 2PE uncaging -- antisecretory factor -- cerebellar granule cells -- GABAA receptor -- patch‐clamp technique -- RuBi‐GABA; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.15775
• Languages: English
• ISSNs: 0953-816X

Abstract

Abstract: The antisecretory factor (AF) is an endogenous protein that counteracts intestinal hypersecretion and various inflammation conditions in vivo. It has been detected in many mammalian tissues and plasma, but its mechanisms of action are largely unknown. To study the pharmacological action of the AF on different GABAA receptor populations in cerebellar granule cells, we took advantage of the two‐photon uncaging method as this technique allows to stimulate the cell locally in well‐identified plasma membrane parts. We compared the electrophysiological response evoked by releasing a caged GABA compound on the soma, the axon initial segment and neurites before and after administering AF‐16, a 16 amino acids long peptide obtained from the amino‐terminal end of the AF protein. After the treatment with AF‐16, we observed peak current increases of varying magnitude depending on the neuronal region. Thus, studying the effects of furosemide and AF‐16 on the electrophysiological behaviour of cerebellar granules, we suggest that GABAA receptors, containing the α6 subunit, may be specifically involved in the increase of the peak current by AF, and different receptor subtype distribution may be responsible for differences in this increase on the cell. Abstract : We report on the effect of antisecretory factor (AF), an endogenous protein that counteracts intestinal hypersecretion and various inflammation conditions, on a specific neuronal receptor (GABAA ) in rat cerebellar granules. We demonstrate that AF acts on a specific type of receptor subunits (α6 ) and that its effect differs in various cell regions. This study contributes to shedding light on the AF mechanism of action on GABAergic transmission, which is still unknown.