Kofuji P, Hofer M, Millen K J, Millonig J H, Davidson N, Lester H A, Hatten M E
Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.
Neuron. 1996 May;16(5):941-52. doi: 10.1016/s0896-6273(00)80117-8.
In the neurological mutant mouse weaver, granule cell precursors proliferate normally in the external germinal layer of the cerebellar cortex, but fail to differentiate. Granule neurons purified from weaver cerebella have greatly reduced G protein-activated inwardly rectifying K+ currents; instead, they display a constitutive Na+ conductance. Expression of the weaver GIRK2 channel in oocytes confirms that the mutation leads to constitutive activation, loss of monovalent cation selectivity, and increased sensitivity to three channel blockers. Pharmacological blockade of the Na+ influx in weaver granule cells restores their ability to differentiate normally. Thus, Na+ flux through the weaver GIRK2 channel underlies the failure of granule cell development in situ.
在神经学突变小鼠“织工鼠”中，颗粒细胞前体在小脑皮质的外生发层中正常增殖，但无法分化。从小脑“织工鼠”中纯化出的颗粒神经元，其G蛋白激活的内向整流钾离子电流大幅减少；相反，它们表现出一种组成型钠电导。在卵母细胞中表达“织工鼠”GIRK2通道证实，该突变导致通道组成型激活、单价阳离子选择性丧失以及对三种通道阻滞剂的敏感性增加。对“织工鼠”颗粒细胞中钠内流进行药理学阻断，可恢复其正常分化的能力。因此，通过“织工鼠”GIRK2通道的钠通量是颗粒细胞原位发育失败的基础。
