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

J Physiol. 2001 Oct 15;536(Pt 2):429-37. doi: 10.1111/j.1469-7793.2001.0429c.xd.

Abstract

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 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 GABA(A) receptor agonist muscimol evoked transient increases in [Ca2+]i in immature PNs. These Ca2+ transients were reversibly abolished by the GABA(A) 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 (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 x 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Bicuculline / pharmacology
  • Calcium / metabolism
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology*
  • Cerebellum / cytology
  • Cerebellum / growth & development
  • GABA Antagonists / pharmacology
  • Gramicidin / pharmacology
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Nickel / pharmacology
  • Patch-Clamp Techniques
  • Purkinje Cells / drug effects
  • Purkinje Cells / metabolism*
  • Rats
  • Rats, Wistar
  • Receptors, GABA-A / metabolism
  • gamma-Aminobutyric Acid / pharmacology*

Substances

  • Anti-Bacterial Agents
  • GABA Antagonists
  • Receptors, GABA-A
  • Gramicidin
  • gamma-Aminobutyric Acid
  • Nickel
  • Calcium
  • Bicuculline