Figure 5. Examples of agonist-induced whole-cell currents elicited at the low-concentration end of the dose-response curve.

A, original traces of currents induced by DMPP, ACh, nicotine and cytisine. Currents were recorded in the same cell by the perforated patch technique as described in Methods, except that application times were extended to 15 s. The cell was voltage clamped at -70 mV. Apart from ACh (4 μM), agonist concentrations for the effects shown were 3 μM. B, dose-response relationship of peak currents constructed from original recordings as shown in A. Data points are mean peak currents measured in duplicate for each agonist. Curves based on eqn (1) were simultaneously fitted to data points by weighted non-linear regression using the ALLFIT routine with the constraints of a shared slope and a fixed maximum as described in Methods. Potency ratios relative to the standard (DMPP, ▵) were 1.33 for cytisine (▿), 0.69 for nicotine (○) and 0.46 for ACh (□). Note that numbers > 1 mean potencies greater than DMPP (i.e. larger effects at equal concentrations). Averaged potency ratios from identically designed experiments are provided in Table 2E. C, dose-response relationship constructed from original recordings as shown in A, but based on a 15 s time integral (i.e. the area under the curve during a 15 s application of agonist) instead of measuring peak currents as shown in B. Data points are mean 15 s time integrals of currents measured in duplicate for each agonist. Potency ratios relative to DMPP (▵) were 1.61 for cytisine (▿), 0.84 for nicotine (○) and 0.57 for ACh (□), calculated by the same method as described in B. Averaged potency ratios from identically designed experiments are provided in Table 2F.