Article Figures & Data
Figures
- Figure 1
Structures of DMPP and PIP compounds.
- Figure 2
Responses of rat α7 (A) and chick α7 nAChRs (B) to the PIP compounds and DMPP. For each oocyte, the ACh control (1 mM) is shown as is the corresponding calibration. All compounds were applied at 1 mM and are representative of four determinations for the PIP series and three determinations for DMPP (A), and eight determinations for the PIP series and six determinations for DMPP (B). The response to 1 mM ACh in the presence of 1 mM ButylPIP was 24 ± 4% of the response to 1 mM ACh alone. Unless otherwise noted, oocytes were clamped at −120 mV in this and all subsequent figures.
- Figure 5
A, Dose-response curves for acetylcholine, DMPP, and ButylPIP. Each point in the dose-response curve to acetylcholine is an average of two to six determinations, with the error bars representing the S.E.M. Lines are a nonlinear least squares fit of the entire data set to the Hill equation for ACh and DMPP. Hill coefficients ranged from 1.3 to 1.55 for ACh and were 1 for DMPP. The fit for ButylPIP included a term for inhibition as well as activation. Also shown are responses of the rat α7 Q84L mutant (B) and chick α7 L84Q mutant (C) to acetylcholine, the PIP compounds, and DMPP. For individual traces, the ACh control (1 mM) is shown as is the corresponding calibration. All compounds in individual traces were applied at 1 mM and are representative of four to five determinations. The response to 1 mM ACh in the presence of 1 mM ButylPIP was 35 ± 3% of the response to 1 mM ACh alone (the trace shown was from a separate oocyte but was normalized to the response to ACh alone in that same oocyte).
- Figure 3
A, response to 1 mM ACh and ButylPIP of the chick L247T mutant α7 receptor (representative of eight determinations). B, responses of the chick wild-type α7 homomeric receptor to 1 mM ACh and 1 mM ButylPIP with the oocyte clamped at +60 mV. EDTA (100 nl of 8 mM) was injected into the oocyte 15 min before recording (representative of five determinations).
- Figure 4
Alignment of several neuronal nAChR subunits. The boxes indicate the positions of conserved sequences thought to participate in the acetylcholine binding site. DMPP is a full agonist for rat α3 (this includes α3β2 and α3β4; Luetje and Patrick, 1991), chick α8, human α7, and rat α7 (Chavez-Noriega et al., 1997; Gerzanich et al., 1994; Séguéla et al., 1993). In these cases, position 84 is Q or K. In the cases of chick α7 (Gerzanich et al., 1994), rat α9 (Elgoyhen et al., 1994), and rat α4 (this includes α4β2 and α4β4; Luetje and Patrick, 1991), DMPP is a weak partial agonist activating less than 20% of the maximal current induced by acetylcholine.
