ERK在杏仁體中央被核神經元細胞興奮性角色探討

Abstract

杏仁體中央被核(CeAC)可接收經由杏仁體-旁臂核(PBA)路徑傳遞，來自腦幹及脊髓的痛覺訊息，同時也接收直接由脊髓投射上來的痛覺訊息，此核區被稱為「痛覺杏仁核」已將近十年，先前研究指出佛波醇12,13-乙酸酯(PDA)可顯著促進旁臂核到CeAC的神經傳導作用，且與細胞內部的胞外訊息傳遞激脢(ERK)有關，本研究使用全細胞紀錄電生理紀錄以及藥理方式探討ERK在調節CeAC神經細胞興奮性上所扮演的角色，給予短期PDA(蛋白激脢C之活化劑)可提高動作電位發生的頻率，然而給予長期PDA卻會降低其頻率；另外短期PDA也會增加Ih-current，但長期PDA則減緩其強度，此外，給予長期PDA也會延遲動作電位發生的時間，在給予蛋白激脢C(PKC)抑制劑－Chelerythrine與GF109203X之後，短期與長期的PDA反應都不復出現，給予U0126不會影響短期PDA帶來的反應，卻逆轉了長期PDA先前的反應情形，實驗結果顯示：(1)給予PDA會經由PKC—ERK路徑作用，在不同的時間條件下，調節CeAC的神經興奮性；(2)活化ERK加劇動作電位延遲發生的情形(A型鉀離子通道)。

The capsular central amygdaloid (CeAC) nucleus acquires nociceptive specific information from the brainstem and spinal cord via the parabrachio-amygdaloid (PBA) pain pathway as well as via direct projections from the spinal cord. It has been termed as “nociceptive amygdala” for almost a decade. Previous study indicated that application of phorbol 12,13-diacetate (PDA) caused marked enhancement of synaptic transmission of parabrachial input onto CeAC nucleus and the elevation of intracellular ERK was involved. In the present study, using patch-clamp technique and pharmacological methods, the role of ERK in regulating neuronal excitability of CeAC was examined. Short-term application of the PKC activator, PDA increased the number of action potentials whereas the long-term application decreased the spike number. Beside, short-term PDA enhanced the size of Ih current but long-term PDA downsized it. In the meanwhile, long-term application of PDA also increased the first spike latency. Protein Kinase C (PKC) inhibitors, Chelerythrine and GF109203X abolished the effect of PDA in both time-scales. Application of U0126 had no effect on short-term PDA however it reversed the effect caused by long term PDA application. The result suggested that (1) PKC—ERK pathway induced by PDA regulated input-output function of neuronal excitability of CeAC in different time-scales; (2) ERK activation enhanced the delay onset of action potential (stongly related to A-type potassium channel).