Effect of Synthetic Aβ Peptide Oligomers and Fluorinated Solvents on Kv1.3 Channel Properties and Membrane Conductance
Figure 6
Effect of HFIP-free Aβ1–42 oligomers (NaOH protocol) on Kv 1.3 current and on BLM conductance.
(A) Representative K+ currents evoked by depolarizing voltage steps from the holding potential of −80 mV before (black) and after (red) Aβ1–42 application. Note, that Aβ1–42 samples aggregated for less than 1 hr and presumably contained monomeric peptide, had no effect on K+ current (A, left), whereas samples aggregated for 48 hrs produced characteristic effect on K+ current kinetics (A, right). (B–E) Activation and inactivation kinetics of K+ currents before (black) and after application of Aβ1–42 oligomers (red) shown in absolute (B, D) and normalized (C, E) values of time constants at different voltages (mean ± S.E.M., n = 4 cells). The effect of Aβ on the activation time constant was significant in Tests of Within-Subjects Effects (F = 34.5; #P = 0.009, Two-way RM-ANOVA) with significant interaction between FactorA (treatment) and FactorB (voltage) (F = 38.03), and by Pairwise Comparisons at −20 mV (*P = 0.006, Tukey test). The effect of Aβ on the inactivation time constant was also significant in Tests of Within-Subjects Effects (F = 19.1; #P = 0.022, Two-way RM-ANOVA) with significant interaction between FactorA (treatment) and FactorB (voltage) (F = 7.1), and by Pairwise Comparisons at −20 mV (*P = 0.016, Tukey test). (F) Representative I/V curves recorded on DOPC/DOPE BLMs before (black) and after (red) application of Aβ1–42 oligomers. (G) Dose-dependence of Aβ-induced currents at +150 mV across BLMs (mean ± S.E.M., n = 5 experiments, out of a total of 12, in which the effect was observed).