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Involvement of Intracellular Stores in the Ca 2+ Responses to N ‐Methyl‐D‐Aspartate and Depolarization in Cerebellar Granule Cells
Author(s) -
Simpson Peter B.,
Challiss R. A. John,
Nahorski Stefan R.
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb02184.x
Subject(s) - depolarization , intracellular , granule (geology) , biophysics , cerebellum , neuroscience , chemistry , biology , biochemistry , paleontology
The [Ca 2+ ] 1 of cerebellar granule cells can be increased in a biphasic manner by addition of NMDA or by depolarization (induced by elevating the extracellular K + level), which both activate Ca 2+ influx. The possibility that these stimuli activate Ca 2+ ‐induced Ca 2+ release was investigated using granule cells loaded with fura 2‐AM. Dantrolene, perfused onto groups of cells during the sustained plateau phase of the [Ca 2+ ] 1 response to K + or NMDA, was found to reduce the response to both agents in a concentration‐dependent manner. Preincubation with thapsigargm (10 μ M ) substantially reduced the plateau phase of the [Ca 2+ ], response to K + and both the peak and plateau phases of the NMDA response. Preincubation with ryanodine (10 μ M ) also reduced both the K + ‐evoked plateau response and both phases of the NMDA response. Neither had a consistent effect on the peak response to K + . The effects of thapsigargin and ryanodine on the NMDA response were partially additive. These results demonstrate that in cerebellar granule cells a major component of both K + ‐ and NMDA‐induced elevation of [Ca 2+ ] 1 appears to be due to release from intracellular stores. The partial additivity of the effects of thapsigargin and ryanodine suggests that these agents affect two overlapping but nonidentical Ca 2+ pools.