Comments on 'A quantitative model of amphetamine action on the serotonin transporter', by Sandtner et al., Br J Pharmacol 171: 1007-1018

Abstract

This article is a Commentary on Sandtner W, Schmid D, Schicker K, Gerstbrein K, Koenig X, Mayer FP, Boehm S, Freissmuth M and Sitte HH (2014). A quantitative model of amphetamine action on the 5-HT transporter. Br J Pharmacol 171: 1007–1018. doi: 10.1111/bph.12520. The authors reply in Schmid et al., (2015). Br J Pharmacol 172: this issue. doi: 10.1111/bph.12766

Figure 1

Persistent current in hDAT-transfected HEK cells. Current through hDAT transiently transfected HEK293 cells. V = −60 mV, T = 37°C. 30 s of 10 μM dopamine (DA) induces an inward current that returns to baseline when dopamine is removed. 30 s of 10 μM S(+)amphetamine (S(+)AMPH) induced a similar inward peak current; however, the return of current upon wash-out of S(+)amphetamine was slower and persists for tens of seconds and up to a minute. Dopamine and S(+)amphetamine are overlaid for better comparison of kinetics. Using a mono-exponential function, we determined the time constants for the current decays: τ_DA = 1.3 s, τ_S(+)AMPH = 5.1 s, τ_S(+)AMPH/τ_DA = 3.8 s.

Figure 2

Persistent current versus polar surface area (PSA). hDAT-expressing oocytes, V = −60 mV, room temperature. All drugs are applied for 60 s and are 10 μM in concentration. The persistent current is given as a fraction of the dopamine-induced current for each oocyte to normalize for expression level from cell to cell. The PSA values were obtained from http://chemicalize.org. Mean ± SEM (n = 5–15).