在(zai)心血(xue)(xue)管(guan)(guan)藥(yao)(yao)(yao)理(li)研(yan)究中(zhong)的(de)(de)(de)應用，隨(sui)(sui)著膜(mo)片鉗(qian)技(ji)(ji)術(shu)在(zai)心血(xue)(xue)管(guan)(guan)方面的(de)(de)(de)廣(guang)泛應用，對血(xue)(xue)管(guan)(guan)疾病和藥(yao)(yao)(yao)物(wu)作用的(de)(de)(de)認識(shi)不(bu)僅得到了(le)不(bu)斷更(geng)新(xin)(xin)(xin)，而(er)且在(zai)其(qi)病因學(xue)與藥(yao)(yao)(yao)理(li)學(xue)方面還形(xing)成了(le)許多新(xin)(xin)(xin)的(de)(de)(de)觀點(dian)。正(zheng)如諾貝爾基(ji)金會在(zai)頒獎時(shi)(shi)所說：“Neher和Sadmann的(de)(de)(de)貢獻(xian)有利于(yu)了(le)解不(bu)同疾病機理(li)，為(wei)研(yan)制(zhi)新(xin)(xin)(xin)的(de)(de)(de)更(geng)為(wei)的(de)(de)(de)藥(yao)(yao)(yao)物(wu)開(kai)辟了(le)道路”。目前在(zai)離子(zi)通道高(gao)通量(liang)(liang)篩選(xuan)中(zhong)主要是進行樣(yang)品量(liang)(liang)大(da)、篩選(xuan)速(su)度占優勢、信息(xi)量(liang)(liang)要求不(bu)太高(gao)的(de)(de)(de)初級篩選(xuan)。近幾(ji)年，分別(bie)形(xing)成了(le)以膜(mo)片鉗(qian)和熒光探(tan)針(zhen)為(wei)基(ji)礎的(de)(de)(de)兩大(da)主流(liu)技(ji)(ji)術(shu)市場。將電(dian)生(sheng)理(li)研(yan)究信息(xi)量(liang)(liang)大(da)、靈敏度高(gao)等(deng)特點(dian)與自(zi)動(dong)化、微量(liang)(liang)化技(ji)(ji)術(shu)相結合(he)，產生(sheng)了(le)自(zi)動(dong)化膜(mo)片鉗(qian)等(deng)一(yi)些(xie)新(xin)(xin)(xin)技(ji)(ji)術(shu)。滔博生(sheng)物(wu)TOP-Bright專(zhuan)注基(ji)于(yu)多種離子(zi)通道靶點(dian)的(de)(de)(de)化合(he)物(wu)體(ti)外篩選(xuan),服務(wu)于(yu)全球藥(yao)(yao)(yao)企的(de)(de)(de)膜(mo)片鉗(qian)公司,快速(su)獲得實驗(yan)結果,專(zhuan)業(ye)團(tuan)隊,7*52小時(shi)(shi)隨(sui)(sui)時(shi)(shi)人工在(zai)線咨詢.一(yi)些(xie)學(xue)者建立了(le)組(zu)織(zhi)切片膜(mo)片鉗(qian)技(ji)(ji)術(shu)（Slicepatch），就能在(zai)哺(bu)乳動(dong)物(wu)腦片制(zhi)備上做(zuo)全細胞記(ji)錄(lu)。日本全細胞膜(mo)片鉗(qian)系統

膜(mo)(mo)(mo)片(pian)鉗(qian)(qian)(qian)技(ji)(ji)(ji)術(shu)的(de)(de)(de)(de)發展(zhan)∶全自(zi)動(dong)(dong)膜(mo)(mo)(mo)片(pian)鉗(qian)(qian)(qian)技(ji)(ji)(ji)術(shu)（Automated patch clamp technique）的(de)(de)(de)(de)出(chu)現(xian)(xian)標(biao)(biao)志著膜(mo)(mo)(mo)片(pian)鉗(qian)(qian)(qian)技(ji)(ji)(ji)術(shu)已經發展(zhan)到了(le)(le)(le)一個(ge)(ge)(ge)嶄新階段(duan)，從這個(ge)(ge)(ge)意義上說，前面(mian)所講的(de)(de)(de)(de)膜(mo)(mo)(mo)片(pian)鉗(qian)(qian)(qian)技(ji)(ji)(ji)術(shu)我們稱之(zhi)為(wei)傳統膜(mo)(mo)(mo)片(pian)鉗(qian)(qian)(qian)技(ji)(ji)(ji)術(shu)（ Traditional patch clamp technique），傳統膜(mo)(mo)(mo)片(pian)鉗(qian)(qian)(qian)技(ji)(ji)(ji)術(shu)每次(ci)只能(neng)記(ji)(ji)(ji)(ji)錄(lu)(lu)一個(ge)(ge)(ge)細(xi)(xi)胞(bao)(bao)（或一對細(xi)(xi)胞(bao)(bao)），對實驗人員來說是(shi)(shi)一項耗時(shi)耗力的(de)(de)(de)(de)工作(zuo)，不適合在藥(yao)物(wu)開(kai)發初期和中(zhong)期進行大(da)量(liang)化(hua)合物(wu)的(de)(de)(de)(de)篩選(xuan)，也不適合需要記(ji)(ji)(ji)(ji)錄(lu)(lu)火量(liang)細(xi)(xi)胞(bao)(bao)的(de)(de)(de)(de)基礎(chu)實驗研究。全自(zi)動(dong)(dong)膜(mo)(mo)(mo)片(pian)鉗(qian)(qian)(qian)技(ji)(ji)(ji)術(shu)的(de)(de)(de)(de)出(chu)現(xian)(xian)在很大(da)程(cheng)度上解決(jue)了(le)(le)(le)這些(xie)問(wen)題，它不僅通(tong)(tong)(tong)量(liang)高，一次(ci)能(neng)記(ji)(ji)(ji)(ji)錄(lu)(lu)幾個(ge)(ge)(ge)甚至幾十個(ge)(ge)(ge)細(xi)(xi)胞(bao)(bao)，而(er)且從找細(xi)(xi)胞(bao)(bao)、形成封接、破膜(mo)(mo)(mo)等整個(ge)(ge)(ge)實驗操作(zuo)實現(xian)(xian)了(le)(le)(le)自(zi)動(dong)(dong)化(hua)，免除了(le)(le)(le)這些(xie)操作(zuo)的(de)(de)(de)(de)復雜與困難。這兩個(ge)(ge)(ge)優點(dian)使(shi)得膜(mo)(mo)(mo)片(pian)鉗(qian)(qian)(qian)技(ji)(ji)(ji)術(shu)的(de)(de)(de)(de)工作(zuo)效(xiao)率提高了(le)(le)(le)!全自(zi)動(dong)(dong)膜(mo)(mo)(mo)片(pian)鉗(qian)(qian)(qian)技(ji)(ji)(ji)術(shu)采用的(de)(de)(de)(de)標(biao)(biao)本必須是(shi)(shi)懸浮細(xi)(xi)胞(bao)(bao)，像腦片(pian)這類標(biao)(biao)本無(wu)法采用。此(ci)外，全自(zi)動(dong)(dong)膜(mo)(mo)(mo)片(pian)鉗(qian)(qian)(qian)技(ji)(ji)(ji)術(shu)只能(neng)進行全細(xi)(xi)胞(bao)(bao)記(ji)(ji)(ji)(ji)錄(lu)(lu)模(mo)式(shi)、穿孔膜(mo)(mo)(mo)片(pian)鉗(qian)(qian)(qian)記(ji)(ji)(ji)(ji)錄(lu)(lu)模(mo)式(shi)以及(ji)細(xi)(xi)胞(bao)(bao)貼(tie)附式(shi)單通(tong)(tong)(tong)道記(ji)(ji)(ji)(ji)錄(lu)(lu)模(mo)式(shi)，而(er)不能(neng)進行其他模(mo)式(shi)的(de)(de)(de)(de)記(ji)(ji)(ji)(ji)錄(lu)(lu)。雙分子層膜(mo)(mo)(mo)片(pian)鉗(qian)(qian)(qian)細(xi)(xi)胞(bao)(bao)功能(neng)特性這是(shi)(shi)一種(zhong)以記(ji)(ji)(ji)(ji)錄(lu)(lu)通(tong)(tong)(tong)過離子通(tong)(tong)(tong)道的(de)(de)(de)(de)離子電流來反映細(xi)(xi)胞(bao)(bao)膜(mo)(mo)(mo)單一的(de)(de)(de)(de)或多個(ge)(ge)(ge)的(de)(de)(de)(de)離子通(tong)(tong)(tong)道分子活(huo)動(dong)(dong)的(de)(de)(de)(de)技(ji)(ji)(ji)術(shu)。

膜(mo)(mo)片鉗(qian)(qian)技術的(de)(de)(de)建立1.拋(pao)光及(ji)填充(chong)好玻璃管(guan)微電(dian)(dian)(dian)(dian)(dian)極(ji)(ji)(ji)，并(bing)將(jiang)它固定在(zai)電(dian)(dian)(dian)(dian)(dian)極(ji)(ji)(ji)夾持(chi)器(qi)(qi)中。2.通過(guo)一(yi)(yi)個(ge)與電(dian)(dian)(dian)(dian)(dian)極(ji)(ji)(ji)夾持(chi)器(qi)(qi)連接(jie)的(de)(de)(de)導管(guan)給微電(dian)(dian)(dian)(dian)(dian)極(ji)(ji)(ji)內一(yi)(yi)個(ge)壓(ya)力，一(yi)(yi)直(zhi)到電(dian)(dian)(dian)(dian)(dian)極(ji)(ji)(ji)浸入記錄(lu)槽(cao)溶(rong)液中。3.當電(dian)(dian)(dian)(dian)(dian)極(ji)(ji)(ji)浸沒在(zai)溶(rong)液中時(shi)給電(dian)(dian)(dian)(dian)(dian)極(ji)(ji)(ji)一(yi)(yi)個(ge)測(ce)定脈沖（命令電(dian)(dian)(dian)(dian)(dian)壓(ya)，如5-10ms，10mV）讀出電(dian)(dian)(dian)(dian)(dian)流(liu)，按照歐姆定律(lv)計(ji)算電(dian)(dian)(dian)(dian)(dian)阻(zu)。4.通過(guo)膜(mo)(mo)片鉗(qian)(qian)放(fang)大(da)器(qi)(qi)的(de)(de)(de)控制鍵將(jiang)微電(dian)(dian)(dian)(dian)(dian)極(ji)(ji)(ji)前列的(de)(de)(de)連接(jie)電(dian)(dian)(dian)(dian)(dian)位(wei)（junctionpotentials）調至零位(wei)，這種電(dian)(dian)(dian)(dian)(dian)位(wei)差是由于電(dian)(dian)(dian)(dian)(dian)極(ji)(ji)(ji)內填充(chong)溶(rong)液與浸浴液不同離子成分的(de)(de)(de)遷移造成的(de)(de)(de)。5.用微操縱器(qi)(qi)將(jiang)微電(dian)(dian)(dian)(dian)(dian)極(ji)(ji)(ji)前列在(zai)直(zhi)視下靠近要記錄(lu)的(de)(de)(de)細(xi)胞(bao)表面，并(bing)觀察電(dian)(dian)(dian)(dian)(dian)流(liu)的(de)(de)(de)變(bian)化，直(zhi)至阻(zu)抗達到1GΩ以(yi)上形成"干兆封接(jie)"6.調整(zheng)靜息膜(mo)(mo)電(dian)(dian)(dian)(dian)(dian)位(wei)到期望的(de)(de)(de)鉗(qian)(qian)位(wei)電(dian)(dian)(dian)(dian)(dian)壓(ya)的(de)(de)(de)水平，使放(fang)大(da)器(qi)(qi)從"搜尋(xun)"轉到"電(dian)(dian)(dian)(dian)(dian)壓(ya)鉗(qian)(qian)"時(shi)細(xi)胞(bao)不至于鉗(qian)(qian)位(wei)到零。

1980年(nian)，Sigworth、Hamill、Neher等在記錄電(dian)(dian)(dian)極內施加負壓(ya)吸引，得(de)到了(le)(le)10~100GΩ的(de)(de)高阻封接（gigaseal），降(jiang)低記錄噪(zao)聲，實(shi)現(xian)了(le)(le)單根電(dian)(dian)(dian)極既鉗制膜(mo)(mo)電(dian)(dian)(dian)位(wei)又記錄單通道(dao)電(dian)(dian)(dian)流。獲1991年(nian)Nobel獎。1955年(nian)，Hodgkin和Keens應用電(dian)(dian)(dian)壓(ya)鉗（Voltageclap）在研(yan)究神經(jing)軸突膜(mo)(mo)對鉀離子通透性時發現(xian)放射性鉀跨軸突膜(mo)(mo)的(de)(de)運動(dong)很像是(shi)通過許多狹窄(zhai)空洞的(de)(de)運動(dong)，并提出了(le)(le)"通道(dao)"的(de)(de)概念。1963年(nian)，描述電(dian)(dian)(dian)壓(ya)門控動(dong)力(li)學的(de)(de)Hodgkin-Hx上模型（簡(jian)稱H-H模型）榮(rong)獲譜貝爾醫(yi)學/生(sheng)理(li)學獎。1976年(nian)，Neher和Sakmann建立膜(mo)(mo)片(pian)鉗（Patchclamp）按術(shu)。1983年(nian)10月，《Single-ChannelRecording》一書(shu)問世(shi)，奠定了(le)(le)膜(mo)(mo)片(pian)鉗技術(shu)的(de)(de)里程碑。1991年(nian)，Neher和Sakmann的(de)(de)膜(mo)(mo)片(pian)鋪技術(shu)榮(rong)獲諾貝爾醫(yi)學/生(sheng)理(li)學獎。膜(mo)(mo)電(dian)(dian)(dian)位(wei)Vm由高輸入阻抗(kang)的(de)(de)電(dian)(dian)(dian)壓(ya)跟隨器所測(ce)量(liang)。

離(li)(li)子通(tong)(tong)道(dao)(dao)(dao)是(shi)一種(zhong)特殊(shu)的(de)(de)(de)膜蛋白，它橫跨(kua)整個膜結構，是(shi)細胞(bao)(bao)內部與(yu)部外(wai)聯系的(de)(de)(de)橋梁和(he)(he)細胞(bao)(bao)內外(wai)物質交(jiao)換的(de)(de)(de)孔(kong)道(dao)(dao)(dao)，當通(tong)(tong)道(dao)(dao)(dao)開放時。細胞(bao)(bao)內外(wai)的(de)(de)(de)一些無機離(li)(li)子如Na，kCa等(deng)(deng)帶電(dian)離(li)(li)子可(ke)(ke)經通(tong)(tong)道(dao)(dao)(dao)順(shun)濃(nong)度(du)梯度(du)或(huo)電(dian)位梯度(du)進行跨(kua)膜擴(kuo)散，從而形成這(zhe)些帶電(dian)離(li)(li)子在(zai)膜內外(wai)的(de)(de)(de)不同(tong)分(fen)布態(tai)勢，這(zhe)種(zhong)態(tai)勢和(he)(he)在(zai)不同(tong)狀(zhuang)態(tai)下的(de)(de)(de)動態(tai)變化是(shi)可(ke)(ke)興奮細胞(bao)(bao)靜息電(dian)位和(he)(he)動作電(dian)的(de)(de)(de)基礎(chu)。這(zhe)些無機離(li)(li)子通(tong)(tong)過離(li)(li)子通(tong)(tong)道(dao)(dao)(dao)的(de)(de)(de)進圍所產生(sheng)的(de)(de)(de)電(dian)活動是(shi)生(sheng)命活動的(de)(de)(de)基礎(chu)，只有(you)在(zai)此基礎(chu)上才可(ke)(ke)能(neng)有(you)腺體分(fen)泌(mi)、肌肉(rou)收縮、基因(yin)表達(da)、新陳(chen)代謝(xie)等(deng)(deng)生(sheng)命活動。離(li)(li)子通(tong)(tong)道(dao)(dao)(dao)結構和(he)(he)功能(neng)障礙決定(ding)了許多疾病的(de)(de)(de)發(fa)生(sheng)和(he)(he)發(fa)展(zhan)。因(yin)此，了解離(li)(li)子通(tong)(tong)道(dao)(dao)(dao)的(de)(de)(de)結構、功能(neng)以及結構與(yu)功能(neng)的(de)(de)(de)關系對于(yu)從分(fen)子水(shui)平深(shen)入探討(tao)某些疾病的(de)(de)(de)病理生(sheng)理機制(zhi)、發(fa)現特異藥(yao)物或(huo)措施等(deng)(deng)均(jun)具有(you)十分(fen)重要的(de)(de)(de)理論和(he)(he)實際意義。膜片鉗技術是(shi)用玻璃(li)微電(dian)極吸(xi)管把(ba)只含1-3個離(li)(li)子通(tong)(tong)道(dao)(dao)(dao)、面積為(wei)幾個平方微米的(de)(de)(de)細胞(bao)(bao)膜通(tong)(tong)過負(fu)壓吸(xi)引封接起來(lai)。全自動膜片鉗

早期的研究(jiu)多使用雙電(dian)極電(dian)壓鉗技術作細(xi)胞(bao)內(nei)電(dian)活動的記錄(lu)。日本(ben)全細(xi)胞(bao)膜片(pian)鉗系(xi)統

膜(mo)片鉗技術(shu)發(fa)展至今，已經(jing)成為(wei)現代(dai)細(xi)胞(bao)電生(sheng)理的(de)(de)(de)常規方法(fa)，它不僅(jin)可以作為(wei)基礎生(sheng)物(wu)(wu)(wu)醫(yi)學(xue)(xue)研究(jiu)的(de)(de)(de)工具，而且(qie)直(zhi)接或(huo)間接為(wei)臨床(chuang)醫(yi)學(xue)(xue)研究(jiu)服務。目(mu)前膜(mo)片鉗技術(shu)廣泛應用(yong)于神經(jing)（腦）科(ke)(ke)學(xue)(xue)、心(xin)血管科(ke)(ke)學(xue)(xue)、藥理學(xue)(xue)、細(xi)胞(bao)生(sheng)物(wu)(wu)(wu)學(xue)(xue)、病理生(sheng)理學(xue)(xue)、中醫(yi)藥學(xue)(xue)、植物(wu)(wu)(wu)細(xi)胞(bao)生(sheng)理學(xue)(xue)、運動(dong)生(sheng)理等多學(xue)(xue)科(ke)(ke)領(ling)域研究(jiu)。隨著全自(zi)動(dong)膜(mo)片鉗技術(shu)（Automaticpatchclamptechnology）的(de)(de)(de)出(chu)現，膜(mo)片鉗技術(shu)因其具有的(de)(de)(de)自(zi)動(dong)化、高通(tong)量特性，在藥物(wu)(wu)(wu)研發(fa)、藥物(wu)(wu)(wu)篩選中顯(xian)示了強勁的(de)(de)(de)生(sheng)命(ming)力。日(ri)本全細(xi)胞(bao)膜(mo)片鉗系統

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