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Patch clamp screening of a7 nAChRs and the temperature dependence of allosteric modulation on nAChR and GABAA
Author(s) -
Haedo Rodolfo Jorge
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.913.45
Subject(s) - allosteric regulation , gabaa receptor , ion channel , allosteric modulator , chemistry , nicotinic agonist , neuroscience , biophysics , ligand gated ion channel , nmda receptor , receptor , biology , biochemistry
The nicotinic acetylcholine receptor (nAChR) is a member of the ligand‐gated ion channel superfamily which includes GABAA, 5HT3, NMDA and glycine receptors. Neuronal nAChR are found in many areas of the mammalian peripheral and central nervous systems including the autonomic ganglia, hippocampus and thalamus. Despite their relative scarcity of expression in the CNS, when activated, nAChR have been shown to have profound effects on cognitive performance, locomotor activity, cardiovascular function and pain perception, amongst others. Additionally, the effect of PNU‐120596 was investigated at physiological temperatures (37 °C), where the current amplitude was significantly smaller, compared with using the same concentrations applied at room temperature. This supports the idea of a strong temperature dependence of the allosteric modulation by PNU‐102596 on nAChRs, also reported by others (Sitzia, Front. Pharmacol. 2011 2: 81). More importantly, we demonstrate for the first time an equal temperature dependence of GABAARs positive allosteric modulators, such as Diazepam, suggesting a general temperature dependence on positive allosteric modulation of ligand‐gated ion channels.