Figure 6.

Each of the five anesthetics studied exhibited different effects on 1^st pulse vs 2^nd pulse GABA_A receptor-mediated inhibition. This was evident in the degree of bicuculline-induced reversal of the depression of first and second pulse responses produced by each anesthetic – for comparable degrees of population spike depression (top bar graph). Isoflurane (350 μM) was least effective at enhancing feedforward inhibition (1st pulse responses), followed by halothane (250 μM), pentobarbital (400 μM), thiopental (80 μM) and propofol (30 μM). In contrast, isoflurane and thiopental were the most effective anesthetics at enhancing feedback inhibition (2nd pulse responses), followed by pentobarbital, halothane, and finally by propofol. Each bar represents the mean ± SD for the percent recovery produced by a maximally effective concentration of bicuculline (10 μM), for at least five experiments. Bicuculline reversal of 1^st vs 2^nd pulse responses were significantly different for isoflurane (p < 0.0001), halothane (p < 0.0001), pentobarbital (p < 0.01), thiopental (p < 0.001), but not for propofol (p > 0.05). There did not appear to be any correlation between the degrees of bicuculline-induced reversal of depression for first vs second pulse responses (bottom graph). There was also not an obvious correlation between lipid solubility vs anesthetic enhanced feedforward or feedback inhibition (not shown). However, lipid solubility did correlate with anesthetic effective concentrations for population spike depression with the following rank order of potency: propofol > thiopental > halothane > isoflurane > pentobarbital.