Figure 7.

Nicotinic agonists act as antagonists at hα6^{(D57N, S156R or N171K)}hβ4hβ3^V9’S-nAChRs. (A) Representative traces are shown for inward or outward current responses from oocytes (voltage clamped at -70 mV) responding to the application of indicated concentrations of nicotine or atropine (shown with the duration of drug exposure as black bars above or below the traces) and expressing hα6hβ4hβ3^V9’S- [(A) (i) and (v)], hα6^D57Nhβ4hβ3^V9’S-[(A) (ii) and (vi)], hα6^S156Rhβ4hβ3^V9’S[(A) (iii) and (vii)] or hα6^N171Khβ4hβ3^V9’S- [(A) (iv) and (viii)] nAChRs. Calibration bars are for 200 (i), 40 [(ii), (iii) and (iv)] or 100 [(v), (vi), (vii) and (viii)] nA currents (vertical) or 5 sec (horizontal). Results for these and other studies were used to estimate mean (±SE) peak outward current responses to 100 μM nicotine (B), 100 μM ACh (C) or 1000 μM atropine (D) from oocytes (n=3-6) heterologously expressing the indicated nAChR subunits. hα6^{(D57N,S156RorN171K)}hβ4hβ3^V9’S-nAChRs elicit outward (positive) current in response to nicotine (B) or ACh (C) which is completely absent from hα6hβ4hβ3^V9’S-nAChRs [(B) and (C)]. hα6^{(D57N,S156RorN171K)}hβ4hβ3^V9’S-nAChRs in rare occasion display minuscule inward currents in response to ACh or nicotine (data not shown). Comparisons between groups were analyzed using one-way ANOVA with Tukey’s post hoc comparison and only those differ from the control (hα6hβ4hβ3^V9’S-nAChR) are marked with asterisks. ***; p < 0.001.