Role of PICK1 in remifentanil-induced miniature excitatory postsynaptic currents mediated by AMPA receptors in spinal dorsal horn neurons and in expression of AMPA receptors in juvenile rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of PICK1 in remifentanil-induced miniature excitatory postsynaptic currents (mEPSCs) mediated by AMPA receptors in spinal dorsal horn neurons and in the expression of AMPA receptors in juvenile rats.Methods Thirty-six male Sprague-Dawley rats,aged 14-18 days,weighing 50-60 g,were used in the study.Eighteen rats were randomly selected,their lumbar segments of the spinal cord were immediately removed,and 108 spinal cord slices (400 μm thick,for wholecell patch-clamp recording) aud 108 spinal cord slices (5 μm thick,for immunofluorescence detection) were prepared.The 108 slices with two kinds of thickness were divided into 3 groups (n=36 each) using a random number tableblank control group (group C),remifentanil group (group R) and remifentanil plus PICK inhibitor group (group R+PlCKi).Spinal cord slices were incubated in artificial cerebrospinal fluid (ACSF) for 90 min in group C.Spinal cord slices were incubated for 90 min in ACSF containing remifentanil at the fiual concentration of 4 mnol/L in group R.Spinal cord slices were incubated for 90 min in ACSF containing remifentanil at the final concentration of 4 nmol/L and 50 μmol PICK inhibitor in group R+PICKi.The whole-cell patch-clamp technique was used to record the amplitude and time interval of AMPA receptors-mediated mEPSCs.The method of immunofluorescence was used to detect the expression of AMPA receptors.Results Compared with group C,the amplitude of mEPSCs was significantly increased,and the time interval of mEPSCs was shortened,the expression of GluR1 and GluR3 was up-regulated,and the expression of GluR2 was down-regulated in R and R+PICKi groups (P＜0.05).Compared with group R,the amplitude of mEPSCs was significantly decreased,and the time interval was prolonged,the expression of GluR3 was down-regulated,the expression of GluR2 was up-regulated (P＜0.05),and no significant change was found in GluR1 expression in group R+PICKi (P＞0.05).Conclusion PICK1 is involved in the process of remifentanil-induced mEPSCs mediated by AMPA receptors in spinal dorsal horn neurons and of expression of AMPA receptors in juvenile rats,which may be the mechanism underlying remifentanil-induced hyperalgesia.