Propofol-induced spike firing suppression is more pronounced in pyramidal neurons than in fast-spiking neurons in the rat insular cortex

Propofol is a major intravenous anesthetic that facilitates GABA_A receptor-mediated inhibitory synaptic currents and modulates inward current (I_h), K⁺, and voltage-gated Na⁺ currents. This propofol-induced modulation of ionic currents changes intrinsic membrane properties and repetitive spike firing in cortical pyramidal neurons. However, it has been unknown whether propofol modulates these electrophysiological properties in GABAergic neurons, which express these ion channels at different levels. This study examined whether pyramidal and GABAergic neuronal properties are differentially modulated by propofol in the rat insular cortical slice preparation. We conducted multiple whole-cell patch-clamp recordings from pyramidal neurons and from GABAergic neurons, which were classified into fast-spiking (FS), low threshold spike (LTS), late-spiking (LS), and regular-spiking nonpyramidal (RSNP) neurons. We found that 100 μM propofol hyperpolarized the resting membrane potential and decreased input resistance in all types of neurons tested. Propofol also potently suppressed, and in most cases eliminated, repetitive spike firing in all these neurons. However, the potency of the propofol-induced changes in membrane and firing properties is particularly prominent in pyramidal neurons. Using a low concentration of propofol clarified this tendency: 30 μM propofol decreased the firing of pyramidal neurons but had little effect on GABAergic neurons. Pre-application of a GABA_A receptor antagonist, picrotoxin (100 μM), diminished the propofol-induced suppression of neural activities in both pyramidal and FS neurons.