Fig. 1.
Pharmacological profile of LvIA(N9R,V10A) for inhibition of human nAChRs expressed in Xenopus oocytes. Oocytes expressing different nAChR subtypes were subjected to two-electrode voltage-clamp electrophysiology, as described in Materials and Methods. LvIA(N9R,V10A) inhibited α3β2, α6/α3β2β3, and β3α6β2α4β2 nAChRs with IC50 values of 3.3 (2.4–4.7) nM (n = 4), 13.5 (8.6–21.2) nM (n = 3), and 11.4 (8.1–16.0) nM (n = 4), respectively. The α6/α3β4 and α6M211L,cytα3β4 constructs were inhibited with IC50 values of 1.0 (0.8–1.3) μM (n = 4) and 2.8 (2.5–3.4) µM, respectively. The peptide also inhibited α4β2 nAChRs with an IC50 of 195 (133–284) nM (n = 4). For α3β4, β4α3β4α3α5(D), and α4β4 nAChRs, the average response after a 5-minute static bath exposure to 10 µM LvIA(N9R,V10A) was 88 ± 4% (n = 4), 98 ± 3 (n = 4), and 97 ± 1% (n = 4), respectively. The error bars denote the S.E.M., and the values in parentheses denote the 95% confidence interval.