Osmotic tension as a possible link between GABA(A) receptor activation and intracellular calcium elevation

Neuron. 2004 Nov 18;44(4):701-13. doi: 10.1016/j.neuron.2004.11.002.


Intracellular calcium concentration rises have been reported following activation of GABA(A) receptors in neonatal preparations and attributed to activation of voltage-dependent Ca(2+) channels. However, we show that, in cerebellar interneurons, GABA(A) agonists induce a somatodendritic Ca(2+) rise that persists at least until postnatal day 20 and is not mediated by depolarization-induced Ca(2+) entry. A local Ca(2+) elevation can likewise be elicited by repetitive stimulation of presynaptic GABAergic afferent fibers. We find that, following GABA(A) receptor activation, bicarbonate-induced Cl(-) entry leads to cell depolarization, Cl(-) accumulation, and osmotic tension. We propose that this tension induces the intracellular Ca(2+) rise as part of a regulatory volume decrease reaction. This mechanism introduces an unexpected link between activation of GABA(A) receptors and intracellular Ca(2+) elevation, which could contribute to activity-driven synaptic plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Signaling / physiology
  • Cerebellum / physiology
  • GABA Agonists / pharmacology
  • Interneurons / physiology*
  • Intracellular Fluid / chemistry
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Muscimol / pharmacology
  • Neuronal Plasticity / physiology
  • Organ Culture Techniques
  • Osmosis / physiology*
  • Rats
  • Receptors, GABA-A / physiology*


  • GABA Agonists
  • Receptors, GABA-A
  • Muscimol
  • Calcium