Figure 4.

Ketamine inhibits ACh responses of the α4β2 and α7 nAChRs in a noncompetitive manner and this inhibition is voltage- and use-dependent in the α4β2 subtype. ACh dose-response curves were normalized to the average response to a saturating concentration of ACh in the absence of ketamine. (A) A concentration-response curve for the activation of α4β2 by varying concentrations of ACh in the absence and presence of 60 μM ketamine. Membrane potential was held at −60 mV (n=5 – 6). (B) A concentration-response curve for the activation of α7 by varying ACh concentrations with and without 25 μM ketamine. Membrane potential was held at −60 mV (n=5 – 6). (C) Voltage response relationship for the α4β2 nAChR inhibition by 60 μM ketamine when activated by 1 mM ACh. At more negative membrane potentials, inhibition is more pronounced (P<0.0001) (n=4 – 7). (D) Voltage response relationship for the α7 nAChR inhibition by 20 μM ketamine when activated by 1 mM ACh. There is no significant voltage-dependence as the slope is not significantly different from zero (P>0.05) (n=4 – 7). (E) Current traces of α4β2 in response to 1 mM ACh before the ketamine application (first), during the first 50 μM ketamine application (second), during the second and third applications of continuous ketamine exposure (third and fourth figures). (F) Current traces of the α7 subtype in response to 1 mM ACh before the ketamine application (first), during the first 50 μM ketamine application (second), during the second and third applications of continuous ketamine exposure (third and fourth figures). Values are mean±s.e.