Atm-deficient mice Purkinje cells show age-dependent defects in calcium spike bursts and calcium currents
Atm-deficient mice Purkinje cells show age-dependent defects in calcium spike bursts and calcium currents
复制标题
DOI：
10.1016/s0306-4522(99)00581-3
复制
发表时间：
2000-01-01
期刊：
影响因子：
3.3
通讯作者：
Tempia, F
中科院分区：
文献类型：
--
作者：
Chiesa, N;Barlow, C;Tempia, F
Ataxia telangiectasia in humans results from homozygous loss-of-function mutations in ATM. Neurological deterioration is the major cause of death in ataxia telangiectasia patients: in the cerebellum, mainly Purkinje cells are affected. We have generated Atm-deficient mice which display neurological abnormalities by several tests of motor function consistent with an abnormality of cerebellar function, but without histological evidence of neuronal degeneration. Here we performed a more detailed morphological analysis and an electrophysiological study on Purkinje cells from Atm-deficient mice of different ages. We found no histological or immunohistochemical abnormalities. Electrophysiology revealed no abnormalities in resting membrane potential, input resistance or anomalous rectification. In contrast, there was a significant decrease in the duration of calcium and sodium firing. The calcium deficit became significant between six to eight and 12-20 weeks of age, and appeared to be progressive. By voltage-clamp recording, we found that the firing deficits were due to a significant decrease in calcium currents, while inactivating: potassium currents seem unaffected. In other mutant mice, calcium current deficits have been shown to be related to cell death.Our experiments suggest that the electrophysiological defects displayed by Atm-deficient mice are early predegenerative lesions and may be a precursor of Purkinje cell degeneration displayed by ataxia telangiectasia patients. (C) 2000 IBRO. Published by Elsevier Science Ltd.
