Jindrichova_2012_PLoS.One_7_e32073

We have examined the effect of temperature on the electrophysiological properties of three neuronal nicotinic acetylcholine receptor (NACHR) subtypes: the rapidly desensitizing homomeric alpha7 nAChR, the more slowly desensitizing heteromeric alpha4beta2 nAChR and on alpha7 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 degrees C) were compared to those recorded at either physiological temperature (37 degrees C) or at lower temperature (4 degrees 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 alpha4beta2 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 alpha7 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 alpha4beta2 and wild type alpha7 nAChRs, the amplitude of alpha7 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 alpha7 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.