Nicotinic acetylcholine receptor model responses to nicotine and acetylcholine.

<p>Response properties of α4β2 (panels A,C,E) and α7 nAChRs (panels B,D,E). (A&B) Dynamics of α4β2- (A) and α7-containing nAChRs (B) in response to Nic. The dynamics of the activation, <i>a</i>, (purple lines) and sensitization, <i>s</i>, (orange lines) are shown during and after the exposure to a constant Nic concentration of 100 µM for 200 ms starting at ms. The normalized receptor activation, , is shown in blue and is proportional to the actual current. The inset shows the dynamics of the same variables on a longer time scale. (C&D) Dose-response curves of α4β2- (C) and α7-containing nAChRs (D) in response to Nic and ACh. The peak current mediated by the receptor during a 200 ms exposure to the respective agonist concentration is shown. The responses to Nic (ACh) are depicted in blue (red). The arrows indicate physiologically relevant nicotine concentrations <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003183#pcbi.1003183-Henningfield1" target="_blank">[11]</a>, <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003183#pcbi.1003183-Rose1" target="_blank">[31]</a>. The half-maximum effective concentrations for ACh-evoked responses are indicated by the dotted black lines. (E) Reduction of the half-maximum response evoked by ACh in the presence of 0.5 µM Nic. The half-maximum effective concentration of the peak current in the absence of Nic is µM for α4β2, and µM for α7 nAChRs (green bars, see C and D). The red bars show the peak current in response to the same ACh concentration in the presence of a constant concentration of µM. See <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003183#pcbi-1003183-t001" target="_blank">Table 1</a> for parameters.