Isoflurane increases the firing rate of retrotrapezoid nucleus Phox2b neurons and may involve the sodium leak channel. (A) Representative trace of firing rate from a chemosensitive retrotrapezoid nucleus neuron shows that exposure to 10% CO₂ or isoflurane increases the neuronal firing rate. (B–E) Summary data indicate that isoflurane at ~0.8 minimum alveolar concentration (MAC; 0.20 to 0.25 mM; B and C) or ~1.5 MAC (0.42 to 0.50 mM; D and E) increases neuronal activity. (F) Comparison of the changed firing rate between ~0.8 MAC and ~1.5 MAC isoflurane (n = 5 or 6 neurons). (G–J) Representative trace of the firing rate (G) and summary data (H–J) indicates that Gd³⁺ (50 μM) can diminish the isoflurane (0.42 to 0.50 mM, ~1.5 MAC)–stimulated firing rate (n = 5 neurons). (K) Isoflurane (0.42 to 0.50 mM, ~1.5 MAC) can depolarize the resting membrane potential of neurons (n = 5 neurons). The data are means ± SD. * P < 0.05, ** P < 0.01, *** P < 0.001 by one-way repeated measures ANOVA (B, D, and H), two-tailed paired t test (C, E, and I–K) or independent samples t test (F).