臺灣博碩士論文加值系統

在中樞神經系統及周邊神經系統發現由酸所活化的電流目前已經歸類為酸敏感性離子通道蛋白質家族所產生。在周邊神經系統裡，酸敏感性離子通道的生理功能主要與痛覺、機械性感覺以及味覺的傳遞有關。然而在中樞神經系統裡，其所扮演的生理功能仍然不清楚。在本實驗裡利用大鼠視叉上核細胞及電生理的方法，發現視叉上核細胞的確實有一種會被酸所活化的ASIC電流。
根據RT-PCR的實驗結果，在視叉上核細胞有表現ASIC 1a、ASIC 2a、ASIC 2b及ASIC 3的mRNA。電生理的實驗則是說明此一電流主要是被細胞外的酸所活化的鈉離子電流，且具有快速去敏化的特性。在藥物學上此種酸所活化的鈉離子電流會對Amiloride具有敏感性，但不會由capsaicin所活化。乳酸及glutathione會增強其電流大小，而DTNB及二價鉛離子會抑制其電流。在生理的角度上，快速給予pH6.4的酸會使細胞膜電位持續去極化並產生密集性的動作電位。因此，ASIC通道可能在中樞神經系統裡的視叉上核細胞扮演著重要的角色。

The conduction of acid-evoked currents in central and sensory neurons is now primarily attributed to a family of proteins called acid-sensing ion channels (ASICs). In peripheral neurons, their physiological function has been linked to nociception, mechanoreception,and taste transduction; however, their role in the CNS remains unclear. This study describes the discovery of a proton-gated current in rat suprachiasmatic nucleus (SCN) termed INa(H+) , which also appears to be mediated by ASICs. RT-PCR confirmed the presence of ASIC mRNA(subunits la,2a,2b,3) in the rat SCN. Electrophysiological investigation showed that all SCN cells respond to rapid extracellular acidification with the activation of a transient Na+ current. INa(H+) desensitizes completely in the continued presence of acid, its current–voltage relationship is linear and its reversal potential shifts with ENa. INa(H+) is reversibly inhibited by amiloride but is not activated by capsaicin . INa(H+) is potentiated by lactate or glutathione but is inhibited by DTNB or Pb2+. Acute application ofpH6.4 to SCN cells causes sustained depolarization and repetitive firing similar to the trains of spontaneous firing rate in these cells. The presence of a proton-gated current in the SCN suggests that ASICs may have a more diverse role in the CNS.

指導教授推薦書………………………………………………………
口試委員會審定書……………………………………………………
長庚大學授權書………………………………………………………iii
誌謝…………………………………………………………………… iv
中文摘要……………………………………………………………… v
英文摘要……………………………………………………………… vi
圖表目錄……………………………………………………………… vii
第一章 序論………………………………………………………… 1
一.視叉上核……………………………………………………… 1
二.能量代謝……………………………………………………… 5
三.酸敏感性離子通道…………………………………………… 10
第二章 實驗材料與方法…………………………………………… 33
第三章 實驗結果…………………………………………………… 41
第四章 討論………………………………………………………… 56
參考文獻……………………………………………………………… 80

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