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GABA‐mediated Ca 2+ signalling in developing rat cerebellar Purkinje neurones
Author(s) -
Eilers Jens,
Plant Tim D.,
Marandi Nima,
Konnerth Arthur
Publication year - 2001
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2001.0429c.xd
Subject(s) - bicuculline , muscimol , gabaa receptor , cerebellum , neuroscience , chemistry , gaba receptor antagonist , agonist , gaba receptor , electrophysiology , synaptic potential , biophysics , receptor , medicine , endocrinology , neurotransmission , biology , biochemistry
1 Cellular responses to GABA A receptor activation were studied in developing cerebellar Purkinje neurones (PNs) in brain slices obtained from 2‐ to 22‐day‐old rats. Two‐photon fluorescence imaging of fura‐2‐loaded cells and perforated‐patch recordings were used to monitor intracellular Ca 2+ transients and to estimate the reversal potential of GABA‐induced currents, respectively. 2 During the 1st postnatal week, focal application of GABA or the GABA A receptor agonist muscimol evoked transient increases in [Ca 2+ ] i in immature PNs. These Ca 2+ transients were reversibly abolished by the GABA A receptor antagonist bicuculline and by Ni 2+ , a blocker of voltage‐activated Ca 2+ channels. 3 Perforated‐patch recordings were used to measure the reversal potential of GABA‐evoked currents ( E GABA ) at different stages of development. It was found that E GABA was about −44 mV at postnatal day 3 (P3), it shifted to gradually more negative values during the 1st week and finally equilibrated at −87 mV at around the end of the 2nd postnatal week. This transition was well described by a sigmoidal function. The largest change in E GABA was −7 mV day −1 , which occurred at around P6. 4 The transition in GABA‐mediated signalling occurs during a period in which striking changes in PN morphology and synaptic connectivity are known to take place. Since such changes were shown to be Ca 2+ dependent, we propose that GABA‐evoked Ca 2+ signalling is one of the critical determinants for the normal development of cerebellar PNs.