The Underlying Mechanism Of T-type Calcium Channel Mediated Emergence Agitation In Neonatal Rats

Objective:To investigate the effect of T-type calcium channels on post-anesthetic emergence agitation in neonatal rats,thus to provide theoretical basis for preventing and decreasing emergence agitation in young patients undergoing sevoflurane anesthesia.Method:According to previous research,neonatal rats after short-period sevoflurane anesthesia could show post-anesthetic hyperactivity behaviors(PAHBs),which can well simulate emergence agitation.Based on PAHBs,we will further explore the mechanism of emergence agitation.Neonatal rats were divided into high-level PAHBs group(P9-11neonatal rats)and low-level PAHBs group(P16-18 neonatal rats).Both of groups were anesthetized with 3%sevoflurane for 10 minutes.The intensity of PAHBs was assessed by PAHBs score scale and open field test.The electroencephalogram was carefully monitored.NNC 55-0396,an antagonist of T-type calcium channels,was injected into lateral ventricles in P10 rats and the changes of PAHBs as well as electroencephalogram were observed.T-type calcium channels mRNA expression level was detected at P5,P10 and P15 rats.Finally,the effect of sevoflurane on T-type calcium channels function at different ages was tested using in-vitro patch-clamp technique.Result:(1)The open field test can well reflect PAHBs intensity.P9-11 neonatal rats showed hyperactive behavior in open field test 1-3 minutes after end of sevoflurane anesthesia.(2)The occurrence of PAHBs was accompanied by increase of theta wave,alpha wave and spike wave in electroencephalogram in P9-11 neonatal rats.(3)PAHBs,as well as theta wave,alpha wave and spike wave were deceased after administration of T-type calcium channels antagonist,NNC 55-0396 in P9-11 neonatal rats.(4)Two subtypes of T-type calcium channels,Ca_v3.2 and Ca_v3.3,were detected in prefrontal cortex.As rats grew up,Ca_v3.2 mRNA expression was decreased and Ca_v3.3 mRNA expression was increased.(5)Sevoflurane could inhibit T-type calcium channels and the inhibition was stronger with higher concentrations of sevoflurane.With increasing age,low-dose sevoflurane could lift T-type calcium channels inhibition level via shifting its activation curve to the right.Conclusion:T-type calcium channels and its’effect on central neural system dysfunction,such as theta wave,alpha wave and spike wave changes,can induce emergence agitation in neonatal rats.