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Changes in temperature have opposing effects on current amplitude in α7 and α4β2 nicotinic acetylcholine receptors.

Jindrichova, M; Lansdell, SJ; Millar, NS; (2012) Changes in temperature have opposing effects on current amplitude in α7 and α4β2 nicotinic acetylcholine receptors. PLoS One , 7 (2) , Article e32073. 10.1371/journal.pone.0032073. Green open access

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Abstract

We have examined the effect of temperature on the electrophysiological properties of three neuronal nicotinic acetylcholine receptor (NACHR) subtypes: the rapidly desensitizing homomeric α7 nAChR, the more slowly desensitizing heteromeric α4β2 nAChR and on α7 nAChRs containing a transmembrane mutation (L247T) that results in dramatically reduced desensitization. In all cases, the functional properties of receptors expressed in Xenopus oocytes at room temperature (RT; 21°C) were compared to those recorded at either physiological temperature (37°C) or at lower temperature (4°C). Alterations in temperature had dramatically differing effects on the amplitude of whole-cell responses detected with these three nAChR subtypes. Compared to responses at RT, the amplitude of agonist-evoked responses with α4β2 nAChRs was increased at high temperature (125±9%, n = 6, P<0.01) and reduced at low temperature (47±5%, n = 6, P<0.01), whereas the amplitude of α7 responses was reduced at high temperature (27±7%, n = 11, P<0.001) and increased at low temperatures (224±16%, n = 10, P<0.001). In contrast to the effects of temperature on α4β2 and wild type α7 nAChRs, the amplitude of α7 nAChRs containing the L247T mutation was unaffected by changes in temperature. In addition, changes in temperature had little or no effect on current amplitude when α7 nAChRs were activated by the largely non-desensitizing allosteric agonist 4BP-TQS. Despite these differing effects of temperature on the amplitude of agonist-evoked responses in different nAChRs, changes in temperature had a consistent effect on the rate of receptor desensitization on all subtypes examined. In all cases, higher temperature resulted in increased rates of desensitization. Thus, it appears that the differing effects of temperature on the amplitudes of whole-cell responses cannot be explained by temperature-induced changes in receptor desensitization rates.

Type: Article
Title: Changes in temperature have opposing effects on current amplitude in α7 and α4β2 nicotinic acetylcholine receptors.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0032073
Publisher version: http://dx.doi.org/10.1371/journal.pone.0032073
Language: English
Additional information: © 2012 Jindrichova et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PMCID: PMC3281115 MJ was supported by a Short Term Fellowship from Federation of European Biochemical Societies (FEBS). SJL was supported by a grant awarded to NSM from The Wellcome Trust (WT085141). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: Animals, Electrophysiological Processes, Humans, Patch-Clamp Techniques, Receptors, Nicotinic, Temperature, Transduction, Genetic, Xenopus laevis
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/1340516
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