本文選題：鉀離子通道　切入點：TASK-1　出處：《河北醫(yī)科大學(xué)》2005年博士論文

【摘要】：中樞化學(xué)感受器(central chemoreceptors, CCRs)在快速調(diào)節(jié)機體酸堿平衡以及內(nèi)環(huán)境穩(wěn)定的過程中發(fā)揮著重要作用。已發(fā)現(xiàn)對化學(xué)性刺激(H+/CO_2)敏感的部位主要位于腦干背側(cè)和腹側(cè)以及中縫核和藍斑等一些神經(jīng)核團。但是腦脊液中的H+/CO2的變化是以何種方式被這些核團感知的?它們又怎樣引起了中樞呼吸沖動發(fā)放的改變?這一系列變化的發(fā)生機理仍然是未解之謎。 早在1989 年就有學(xué)者提出,對化學(xué)刺激敏感的神經(jīng)元的去極化反應(yīng)是由于在靜息狀態(tài)下開放的K~+通道被抑制所導(dǎo)致的。此種存在于細胞膜上的K~+通道的電流變化可能是CCRs 對酸堿刺激做出反應(yīng)的分子基礎(chǔ)。近年發(fā)現(xiàn)的兩孔道K~+通道TASK-1(TWIK-related acid-sensitive K~+ channel-1;TWIK, for tandem P domains in a weak inwardly rectifying K+)就是一種對生理狀態(tài)下細胞外液pH 值敏感的,且在靜息狀態(tài)下開放的外向整流型K~+通道。這種離子通道在腦干多種神經(jīng)元上都有表達,并對五羥色胺(5-HT)、去甲腎上腺素(NE)、P 物質(zhì)等一些與呼吸調(diào)節(jié)相關(guān)的神經(jīng)遞質(zhì)敏感。因此推測TASK-1 可能是存在于中樞的化學(xué)感受器分子,當(dāng)細胞外pH 值降低時,可通過增加細胞的興奮性而使呼吸活動增強。 睡眠呼吸暫停綜合征(sleep apnea syndrome, SAS)是一種嚴(yán)重危害人類身體健康的疾病。目前研究發(fā)現(xiàn)呼吸暫停的發(fā)生與中樞呼吸調(diào)控不穩(wěn)有關(guān),而且這種調(diào)控不穩(wěn)可能來自于中樞化學(xué)感受器敏感性的異常。聯(lián)系TASK-1 的通道特性以及在中樞一些特定神經(jīng)元上的存在,我們推測TASK-1 的表達量及功能的變化可能參與了SAS 的發(fā)病。 因此,本次研究工作將首先系統(tǒng)觀察TASK-1 mRNA 在腦干呼吸相關(guān)神經(jīng)元上的表達情況并觀察TASK-1 的通道電流特性,從解剖學(xué)分布和電生理學(xué)特性上初步判斷TASK-1 與中樞呼吸調(diào)控之間可能存在的關(guān)系。然后通過分析TASK-1 mRNA 在低位腦干上表達量與Sprague-Dawley (SD)大鼠睡眠呼吸暫停指數(shù)之間的相關(guān)性,探討TASK-1 與睡眠呼吸暫停之間
[Abstract]:Central chemoreceptor (CCRs) plays an important role in the rapid regulation of acid-base balance and stability of the internal environment. It has been found that the sites sensitive to chemical stimuli are mainly located in the dorsal and ventral side of the brain stem. Some neuronuclei, such as raphe nuclei and locus coeruleus, but in what way are changes in H / CO _ 2 in cerebrospinal fluid perceived by these nuclei? How do they cause changes in central respiratory impulses? The mechanism of this series of changes is still a mystery. As early as 1989 years ago, some scholars suggested, The depolarization of chemically sensitive neurons is due to the inhibition of open K ~ channels in the resting state. This current change of K ~ channel in the cell membrane may be a reaction of CCRs to the acid-base stimulation. In recent years, the two-channel K ~ channel TASK-1(TWIK-related acid-sensitive K ~ channel-1, for tandem P domains in a weak inwardly rectifying K) is sensitive to the pH value of extracellular fluid in physiological state. And open outward rectifier K ~ channels at rest, which are expressed in a variety of neurons in the brain stem. Some neurotransmitters related to respiratory regulation, such as serotonin 5-HT, norepinephrine and so on, are sensitive to respiratory regulation. Therefore, we speculate that TASK-1 may be a chemoreceptor molecule in the central nervous system, when the extracellular pH decreases, Respiratory activity can be enhanced by increasing cell excitability. Sleep apnea syndrome (Sass) is a disease that seriously endangers human health. Recent studies have found that apnea is associated with unstable central respiratory regulation. Furthermore, this regulatory instability may be due to the abnormal sensitivity of central chemosensors. In connection with the channel characteristics of TASK-1 and the presence of specific neurons in the central nervous system, we speculate that the changes in the expression and function of TASK-1 may be involved in the pathogenesis of SAS. Therefore, the expression of TASK-1 mRNA in brain stem respiratory related neurons and the channel current characteristics of TASK-1 were observed systematically in this study. The possible relationship between TASK-1 and central respiratory regulation was preliminarily determined in terms of anatomical distribution and electrophysiological characteristics, and then the correlation between the expression of TASK-1 mRNA on the low brainstem and the sleep apnea index of Sprague-Dawley rats was analyzed. Study on the relationship between TASK-1 and sleep apnea
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2005
【分類號】：R363

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本文編號：1667866