Hurlock Edward C, McMahon Anne, Joho Rolf H
Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
J Neurosci. 2008 Apr 30;28(18):4640-8. doi: 10.1523/JNEUROSCI.5486-07.2008.
The fast-activating/deactivating voltage-gated potassium channel Kv3.3 (Kcnc3) is expressed in various neuronal cell types involved in motor function, including cerebellar Purkinje cells. Spinocerebellar ataxia type 13 (SCA13) patients carrying dominant-negative mutations in Kcnc3 and Kcnc3-null mutant mice both display motor incoordination, suggested in mice by increased lateral deviation while ambulating and slips on a narrow beam. Motor skill learning, however, is spared. Mice lacking Kcnc3 also exhibit muscle twitches. In addition to broadened spikes, recordings of Kcnc3-null Purkinje cells revealed fewer spikelets in complex spikes and a lower intraburst frequency. Targeted reexpression of Kv3.3 channels exclusively in Purkinje cells in Kcnc3-null mice as well as in mice also heterozygous for Kv3.1 sufficed to restore simple spike brevity along with normal complex spikes and to rescue specifically coordination. Therefore, spike parameters requiring Kv3.3 function in Purkinje cells are involved in the ataxic null phenotype and motor coordination, but not motor learning.
快速激活/失活的电压门控钾通道Kv3.3（Kcnc3）在包括小脑浦肯野细胞在内的参与运动功能的多种神经元细胞类型中表达。携带Kcnc3显性负性突变的脊髓小脑共济失调13型（SCA13）患者以及Kcnc3基因敲除突变小鼠均表现出运动不协调，在小鼠中表现为行走时侧向偏差增加以及在狭窄横梁上滑倒。然而，运动技能学习未受影响。缺乏Kcnc3的小鼠还表现出肌肉抽搐。除了宽峰外，对Kcnc3基因敲除的浦肯野细胞的记录显示，复合峰中的小峰较少，且爆发内频率较低。在Kcnc3基因敲除小鼠以及同样对Kv3.1杂合的小鼠中，仅在浦肯野细胞中靶向重新表达Kv3.3通道足以恢复简单峰的短暂性以及正常的复合峰，并特异性地挽救协调性。因此，浦肯野细胞中需要Kv3.3功能的峰参数参与了共济失调基因敲除表型和运动协调，但不参与运动学习。
