Fig. 4.

α-Ctx BuIA(T5A,P6O), but not LvIA(N9R,V10A), potently inhibits ACh-evoked currents in human adrenal chromaffin cells. Chromaffin cells were isolated from human adrenal glands and subjected to perforated patch-clamp electrophysiology, as described in Materials and Methods. (A) BuIA(T5A,P6O) inhibited ACh-evoked currents with an IC₅₀ of 46.8 (39.8–55.1) nM (n = 7); the Hill slope was −0.98 (0.85–1.1). LvIA(N9R,V10A) inhibited ACh-evoked currents with an IC₅₀ value >1 μM (n = 4). The error bars denote the S.E.M., and the values in parentheses denote the 95% confidence intervals. (B) Representative traces for the inhibition of ACh-evoked currents by increasing concentrations of BuIA(T5A,P6O) and (C) LvIA(N9R,V10A). (D and E) Representative traces showing the inhibition of ACh-evoked currents by both α-Ctxs when tested in the same cell. The LvIA analog inhibited ACh-evoked currents by 7 ± 2% (n = 6), and after washout the BuIA analog inhibited the currents by 98.0 ± 0.3% (n = 6). Values are S.E.M. In (D and E), the LvIA and BuIA analogs are denoted with an asterisk for brevity. Control responses to ACh in the absence of α-Ctxs are shown in red.