If you’ve ever had major surgery, you probably remember lying down and waking up–but nothing in between. Thanks to the anesthesiologist, during the actual surgery you were out of it: immobilized and insensitive to pain. But until recently scientists had little understanding of how anesthetics actually work on the cellular level.
That’s changed thanks to recent experiments performed by researchers at the University of Zurich, in Switzerland. They knew that anesthetics caused pain receptors in the brain to turn off by acting like most drugs do: anesthetizing drugs attach to particular sites on nerve cells and turn them off. The question was, where on nerve cells do these drugs attach?
Nerve cell membranes have receptors for different kinds of chemicals produced by the brain. Gamma-amino butyric acid, or GABA, for example, is a chemical that shuts down nerve cells. The hypothesis was that general anesthesia works by binding to GABA receptors on a nerve cell, thereby activating the receptor and instructing the cell to shut down. So it made sense for the Zurich researchers to focus on GABA receptors.
To do this they worked with mice that had been genetically engineered to have nerve cells with GABA receptors that wouldn’t respond to anesthetics. And sure enough, when such mice were given anesthetic drugs they weren’t nearly as immune to pain as regular mice that had also been given pain-blocking drugs. Clearly, GABA receptor sites on nerve cells are part of what allows anesthetics to do their job.
While the Zurich experiment fills in only one piece of the puzzle, it is an important step towards learning how these amazing drugs work, and how to make them even better.
失去知覺之后
如果你曾經(jīng)做過重大手術(shù),那么你肯定只記得躺下去和醒來這么2個(gè)動(dòng)作,而其間過程是渾然不知的。多虧了麻醉師,你才能在手術(shù)中無知覺地度過:不能動(dòng)彈,也感覺不到疼痛。但是直到最近科學(xué)家們才多少了解到麻醉藥是如何在細(xì)胞層面上工作的。
還得感謝瑞士蘇黎世大學(xué)的研究員們最近做的實(shí)驗(yàn),這一困惑才得以解開。他們弄清楚了麻藥是通 過關(guān)閉大腦中的疼痛接收器才使人感覺不到疼痛,原理跟大多數(shù)藥物一樣:麻藥附著在神經(jīng)細(xì)胞上某個(gè)特殊位置,然后將感知功能關(guān)閉。問題是,麻藥到底附著在什么位置呢?
神經(jīng)細(xì)胞膜有多個(gè)接收器來識別大腦產(chǎn)生的不同類別的化學(xué)物質(zhì)。例如γ-氨基丁酸,或者簡寫為GABA,就是可以關(guān)閉神經(jīng)細(xì)胞感知功能的化學(xué)物質(zhì)。假設(shè)全身麻醉是將麻藥和在神經(jīng)細(xì)胞上的GABA接收器綁定在一起,從而激活接收器,然后再傳達(dá)閉接收功能的指令關(guān)的。這樣的假設(shè)就使蘇黎世大學(xué)的研究員們明白,集中精力研究GABA接收器是關(guān)鍵所在。
為了證明這點(diǎn),他們用基因改造過的老鼠做實(shí)驗(yàn),這種老鼠身上的 GABA接收器對麻藥免疫。毫無疑問,這樣的老鼠在使用了麻藥后,比起正常的用了麻藥的老鼠,疼痛感幾乎沒有降低。顯然位于神經(jīng)細(xì)胞上的GABA接收器是讓麻藥起作用的原因之一。