Calcium dynamics and electrophysiological properties of cerebellar Purkinje cells in SCA1 transgenic mice

Takafumi Inoue, Xi Lin, Kristi A. Kohlmeier, Harry T. Orr, Huda Y. Zoghbi, William N. Ross

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45 Citations (Scopus)

Abstract

Cerebellar Purkinje cells (PCs) from spinocerebellar ataxia type 1 (SCA1) transgenic mice develop dendritic and somatic atrophy with age. Inositol 1,4,5-trisphosphate receptor type 1 and the sarco/endoplasmic reticulum Ca2+ ATPase pump, which regulate [Ca2+]i, are expressed at lower levels in these cells compared with the levels in cells from wild-type (WT) mice. To examine PCs in SCA1 mice, we used whole-cell patch clamp recording combined with fluorometric [Ca2+]i and [Na+]i measurements in cerebellar slices. PCs in SCA1 mice bad Na+ spikes, Ca2+ spikes, climbing fiber (CF) electrical responses, parallel fiber (PF) electrical responses, and metabotropic glutamate receptor (mGluR)-mediated, PF-evoked Ca2+ release from intracellular stores that were qualitatively similar to those recorded from WT mice. Under our experimental conditions, it was easier to evoke the mGluR-mediated secondary [Ca2+]i increase in SCA01 PCs. The membrane resistance of SCA1 PCs was 3.3 times higher than that of WT cells, which correlated with the 1.7 times smaller cell body size. Most SCA1 PCs (but not WT) had a delayed onset (about 50-200 ms) to Na+ spike firing induced by current injection. This delay was increased by hyperpolarizing prepulses and was eliminated by 4-aminopyridine, which suggests that this delay was due to enhancement of the A-like K+ conductance in the SCA1 PCs. In response to CF stimulation, most PCs in mutant and WT mice had rapid, widespread [Ca2+]i changes that recovered in <200 ms. Some SCA1 PCs showed a slow, localized, secondary Ca2+ transient following the initial CF Ca2+ transient, which may reflect release of Ca2+ from intracellular stores. Thus, with these exceptions, the basic physiological properties of mutant PCs are similar to those of WT neurons, even with dramatic alteration of their morphology and downregulation of Ca2+ handling molecules.

Original languageEnglish
Pages (from-to)1750-1760
Number of pages11
JournalJournal of Neurophysiology
Volume85
Issue number4
Publication statusPublished - 2001 Apr 19
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

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    Inoue, T., Lin, X., Kohlmeier, K. A., Orr, H. T., Zoghbi, H. Y., & Ross, W. N. (2001). Calcium dynamics and electrophysiological properties of cerebellar Purkinje cells in SCA1 transgenic mice. Journal of Neurophysiology, 85(4), 1750-1760.