Départment de Pathologie et Biologie Cellulaire, Groupe de Recherche sur le Système Nerveux Central et Centre d'Excellence en Neuromique de l'Université de Montéral, Université de Montréal, Montreal, Quebec, Canada.
J Neurophysiol. 2012 Jul;108(1):148-59. doi: 10.1152/jn.00839.2011. Epub 2012 Apr 4.
The molecular and physiological basis of the touch-unresponsive zebrafish mutant fakir has remained elusive. Here we report that the fakir phenotype is caused by a missense mutation in the gene encoding voltage-gated calcium channel 2.1b (CACNA1Ab). Injection of RNA encoding wild-type CaV2.1 restores touch responsiveness in fakir mutants, whereas knockdown of CACNA1Ab via morpholino oligonucleotides recapitulates the fakir mutant phenotype. Fakir mutants display normal current-evoked synaptic communication at the neuromuscular junction but have attenuated touch-evoked activation of motor neurons. NMDA-evoked fictive swimming is not affected by the loss of CaV2.1b, suggesting that this channel is not required for motor pattern generation. These results, coupled with the expression of CACNA1Ab by sensory neurons, suggest that CaV2.1b channel activity is necessary for touch-evoked activation of the locomotor network in zebrafish.
fakir 突变体的触觉无反应的分子和生理基础仍然难以捉摸。在这里，我们报告 fakir 表型是由电压门控钙通道 2.1b (CACNA1Ab) 基因编码的错义突变引起的。编码野生型 CaV2.1 的 RNA 的注射恢复了 fakir 突变体的触觉反应，而通过 morpholino 寡核苷酸对 CACNA1Ab 的敲低则再现了 fakir 突变体的表型。fakir 突变体在神经肌肉接头处显示正常的电流诱发的突触通讯，但触觉诱发的运动神经元激活减弱。NMDA 诱发的虚拟游泳不受 CaV2.1b 缺失的影响，表明该通道对于运动模式生成不是必需的。这些结果，加上感觉神经元表达 CACNA1Ab，表明 CaV2.1b 通道活性对于斑马鱼中触觉激活运动网络是必需的。
