Effect of propofol on excitability of pyramidal neurons in orbitofrontal cortex of mice and underlying ion channel mechanism / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the effect of propofol on excitability of pyramidal neurons in orbitofrontal cortex of mice and the underlying ion channel mechanism.Methods:Brain slices of 400 μm thickness from healthy male C57 mice (aged 8-12 weeks)were prepared.This experiment was performed in two parts.Part Ⅰ The brain slices were divided into 2 groups ( n=7 each) based on the random number table method: control group (C group) and propofol group (P group). Cells were perfused with vehicle in group C and with 10 μmol/L propofol in group P. Part Ⅱ The brain slices were divided into 5 groups ( n=8 each) using the random number table method: propofol group (P group), hyperpolarization-activated non-selective cation channel antagonist ZD7288 plus propofol group (Z + P group), inward rectifier potassium channel antagonist topiramate plus propofol group(T + P group), transient activation of voltage-gated potassium channel antagonist 4-aminopyridine (4AP) plus propofol group (A + P group), and delayed activation of voltage-gated potassium channel antagonist tetraethylammonium (TEA) plus propofol group (TEA + P group). Cells were perfused with 10 μmol/L propofol for 2 min in P group, with 5 μmol/L ZD7288 and 10 μmol/L melatonin for 2 min in Z+ P group, with 5 μmol/L topiramate and 10 μmol/L propofol for 2 min in T + P group, with 10 μ mol/L 4-aminopyridine and 10 μmol/L propofol for 2 min in A+ P group, and with 10 μmol/L TEA and 10 μmol/L propofol for 2 min in TEA+ P group.The whole-cell currents, membrane potential and discharge frequency of pyramidal neurons in the orbitofrontal cortex were recorded by whole-cell patch-clamp. Results:Part Ⅰ Compared with C group, whole-cell currents were significantly increased, and the membrane potential and discharge frequency were decreased in P group ( P<0.01). Part Ⅱ Compared with P group, no significant change was found in the whole-cell currents, membrane potentials and discharge frequency in Z+ P group, T+ P group and A+ P group ( P>0.05), and the whole-cell currents were significantly decreased, and the membrane potentials and discharge frequency were increased in TEA+ P group ( P<0.05). Conclusion:Propofol can inhibit the excitability of pyramidal neurons in the orbitofrontal cortex, and the mechanism is related to activating delayed activation of voltage-gated potassium channels in mice.