據(jù)一項(xiàng)發(fā)表于11月18日J(rèn)ournal of Neurophysiology網(wǎng)絡(luò)版的研究報(bào)告,,美國普渡大學(xué)的醫(yī)學(xué)科學(xué)院Wenjing Sun等人通過對豚鼠脊髓組織實(shí)驗(yàn),,發(fā)現(xiàn)實(shí)驗(yàn)性藥物4-氨基-3甲基氫氧化物(4-aminopyridine-3-methyl hydroxide)能夠恢復(fù)脊髓損傷造成的神經(jīng)細(xì)胞軸突的功能損壞。
實(shí)驗(yàn)中所采用的藥物是4-氨基吡啶(4-aminopyridine)的衍生物,,4-氨基吡啶最初用于控制多發(fā)性硬化癥的癥狀。研究人員對豚鼠脊髓組織模擬通常情況下的壓迫損傷,然后用4-氨基-3甲基氫氧化物治療損傷的軸突,。
神經(jīng)元的軸突的周圍包圍著髓鞘,具有絕緣作用,,可以防止神經(jīng)沖動(dòng)向周圍擴(kuò)散,,以保證傳導(dǎo)的準(zhǔn)確性。當(dāng)脊髓發(fā)生損傷后,,會(huì)破壞髓鞘的結(jié)構(gòu),,從而使軸突上的傳導(dǎo)神經(jīng)沖動(dòng)的“快速鉀離子通道(fast potassium channels)”受損。
研究人員通過“膜片鉗技術(shù)(patch clamp)”測量信號傳導(dǎo),,發(fā)現(xiàn)4-氨基-3甲基氫氧化物是一種“鉀離子通道阻滯劑”,,能夠防止因髓鞘破壞引起的神經(jīng)沖動(dòng)向周圍擴(kuò)散,從而加強(qiáng)受損傷的脊髓的神經(jīng)傳導(dǎo),。(生物谷Bioon.com)
生物谷推薦原始出處:
J Neurophysiol (November 18, 2009). doi:10.1152/jn.00154.2009
A novel potassium channel blocker, 4-AP-3-MeOH, inhibits fast potassium channels and restores axonal conduction in injured guinea pig spinal cord white matter
Wenjing Sun1, Daniel Smith1, Yan Fu1, Ji-Xin Cheng1, Steven Bryn1, Richard Borgens1, and Riyi Shi1*
1 Purdue University
* To whom correspondence should be addressed.
We have demonstrated that 4-AP-3-MeOH, a 4-aminopyridine derivative, significantly restores axonal conduction in stretched spinal cord white mater strips, and shows no preference in restoring large and small axons. This compound is10 times more potent when compared to 4-AP and other derivatives in restoring axonal conduction. Unlike 4-AP, 4-AP-3-MeOH can restore axonal conduction without changing axonal electrophysiological properties. In addition, we also have confirmed that 4-AP-3-MeOH is indeed an effective blocker of IA based on patch clamp studies using guinea pig dorsal root ganglia cells. Furthermore, we have also provided the critical evidence to confirm the unmasking of potassium channels following mechanical injury. Taken together, our data further support and implicates the role of potassium channels in conduction loss and its therapeutic value as an effective target for intervention to restore function in spinal cord trauma. Furthermore, due to its high potency and possible low side effect of impacting electrophysiological properties, 4-AP-3-MeOH is perhaps the optimal choice in reversing conduction block in spinal cord injury compared to other derivatives previously reported from this group.