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

- Propofol-induced modulation of electrophysiological properties were compared between pyramidal and GABAergic neurons.
- Propofol hyperpolarized the resting membrane potential with a decrease in the input resistance in all cell subtypes.
- Propofol also suppressed repetitive spike firing in all cell subtypes.
- The degree of the propofol-induced changes in the membrane and firing properties was most potent in pyramidal neurons.
- Potentiation of GABAA receptor-mediated tonic currents by propofol contributes to modulation of these membrane properties.

Propofol is a major intravenous anesthetic that facilitates GABAA receptor-mediated inhibitory synaptic currents and modulates inward current (Ih), 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 GABAA receptor antagonist, picrotoxin (100 μM), diminished the propofol-induced suppression of neural activities in both pyramidal and FS neurons. These results suggest that GABAergic neurons, especially FS neurons, are less affected by propofol than are pyramidal neurons and that propofol-induced modulation of the intrinsic membrane properties and repetitive spike firing are principally mediated by GABAA receptor-mediated tonic currents