GABA‐mediated Ca2+ signalling in developing rat cerebellar Purkinje neurones

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Abstract
1 Cellular responses to GABAA 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 Ca2+ transients and to estimate the reversal potential of GABA-induced currents, respectively. 2 During the 1st postnatal week, focal application of GABA or the GABAA receptor agonist muscimol evoked transient increases in [Ca2+]i in immature PNs. These Ca2+ transients were reversibly abolished by the GABAA receptor antagonist bicuculline and by Ni2+, a blocker of voltage-activated Ca2+ channels. 3 Perforated-patch recordings were used to measure the reversal potential of GABA-evoked currents (EGABA) at different stages of development. It was found that EGABA 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 EGABA 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 Ca2+ dependent, we propose that GABA-evoked Ca2+ signalling is one of the critical determinants for the normal development of cerebellar PNs.