Propofol inhibited the excitability of pyramidal neurons in the orbitofrontal cortex by influencing the delayed rectifier K+ channels and γ-aminobutyric acid type A receptors.

Propofol anesthesia caused loss of consciousness and cognitive decline. The neural mechanism for this phenomenon still remains elusive. Orbitofrontal cortex (OFC) plays a crucial role in controlling arousal and cognitive flexibility. Using whole-cell patch-clamp recordings, we found that propofol generated an outward current and remarkably inhibited the firing rates of the pyramidal neurons in the OFC. Propofol-induced outward current in the OFC was mediated by activation of delayed rectifier K channels. In addition, propofol enhanced the γ-aminobutyric acid-ergic inhibitory inputs by affecting the γ-aminobutyric acid type A receptors, but not affected the glutamatergic transmissions. The inhibitory effect of propofol in the OFC might reflect a mechanism for the propofol-induced anesthesia. Given the crucial role of the OFC in cognition, these results may also provide useful cues to explain propofol-induced cognitive decline.